Role of Mitogen activated-kinase (MAPK)-phosphatase (MKP)-5 in pulmonary fibrosis.
s A Abstract Mitogen-activated protein kinase (MAPK) phosphatase-5 (MKP-5), is a member of the dual-specificity family of protein tyrosine phosphatases, which negatively regulates p38 MAPK and the c-Jun NH2 kinase (JNK). MKP-5-deficient mice exhibit improved muscle repair and reduced fibrosis in an animal model of muscular dystrophy. Here, we asked whether the effects of MKP-5 on muscle fibrosis extends to other tissues. Using a bleomycin-induced model of pulmonary fibrosis, we found that MKP-5-deficient mice were protected from the development of lung fibrosis and expressed reduced levels of hydroxyproline and fi...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - September 4, 2019 Category: Cytology Authors: Xylourgidis N, Min K, Ahangari F, Yu G, Herazo-Maya JD, Karampitsakos T, Aidinis V, Binzenhöfer L, Bennett AM, Kaminski N, Tzouvelekis A Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

CARM1 regulates senescence during airway epithelial cell injury in COPD pathogenesis.
ml; Abstract Chronic obstructive pulmonary disease (COPD) is a life-threatening lung disease. Although cigarette smoke was considered the main cause of development, the heterogeneous nature of the disease leaves it unclear whether other factors contribute to the predisposition or impaired regeneration response observed. Recently, epigenetic modification has emerged to be a key player in the pathogenesis of COPD. The addition of methyl groups to arginine residues in both histone and non-histone proteins by protein arginine methyltransferases (PRMTs), is an important posttranslational epigenetic modification event r...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - August 28, 2019 Category: Cytology Authors: Sarker RSJ, Conlon TM, Morrone C, Srivastava B, Konyalilar N, Verleden SE, Bayram H, Fehrenbach H, Yildirim AÖ Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Nur77 limits endothelial barrier disruption to LPS in the mouse lung.
In this study, we found that Nur77 is expressed at high levels in the lung and its expression is markedly upregulated in response to LPS administration. While the pulmonary vasculature of mice that lacked Nur77 appeared to function normally under homeostatic conditions, we observed a dramatic decrease in its barrier functions after exposure to LPS, as demonstrated by an increase in serum proteins in the bronchoalveolar lavage fluid and a reduction in the expression of endothelial junctional proteins;VE-cadherin and β-catenin. Similarly, we found that siRNA knockdown of Nur77 in lung microvascular endothelial cells als...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - August 28, 2019 Category: Cytology Authors: Zhu N, Zhang GX, Yi B, Guo ZF, Jang S, Yin Y, Yang F, Summer R, Sun J Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Regulation of Mitochondrial Fragmentation in Microvascular Endothelial Cells Isolated from the Su5416/Hypoxia model of Pulmonary Arterial Hypertension.
Abstract Pulmonary arterial hypertension (PAH) is a morbid disease characterized by progressive right ventricle (RV) failure due to elevated pulmonary artery pressures (PAP). In PAH, histologically complex vaso-occlusive lesions in the pulmonary vasculature contribute to elevated PAP. However, the mechanisms underlying dysfunction of the microvascular endothelial cells (MVECs) that comprise a significant portion of these lesions are not well understood. We recently showed that MVECs isolated from the rat Sugen/Hypoxia (SuHx) experimental model of PAH (SuHx-MVECs) exhibit increases in: migration/proliferation, mito...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - August 28, 2019 Category: Cytology Authors: Suresh K, Servinsky L, Jiang H, Bigham Z, Zaldumbide J, Huetsch JC, Kliment C, Acoba MG, Kirsch BJ, Claypool SM, Le A, Damarla M, Shimoda LA Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Loss of endothelial sulfatase-1 after experimental sepsis attenuates subsequent pulmonary inflammatory responses.
dt EP Abstract Sepsis patients are at increased risk for hospital-acquired pulmonary infections, potentially due to post-septic immunosuppression known as the compensatory anti-inflammatory response syndrome (CARS). CARS has been attributed to leukocyte dysfunction, with an unclear role for endothelial cells. The pulmonary circulation is lined by an endothelial glycocalyx, a heparan sulfate-rich layer essential to pulmonary homeostasis. Heparan sulfate degradation occurs early in sepsis, leading to lung injury. Endothelial synthesis of new heparan sulfates subsequently allows for glycocalyx reconstitution and endo...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - August 28, 2019 Category: Cytology Authors: Oshima K, Han X, Ouyang Y, El Masri R, Yang Y, Haeger SM, McMurtry SA, Lane TC, Davizon-Castillo P, Zhang F, Yue X, Vivès RR, Linhardt RJ, Schmidt EP Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

GDF15 is an epithelial-derived biomarker of idiopathic pulmonary fibrosis.
Abstract Idiopathic pulmonary fibrosis (IPF) is the most common and devastating of the interstitial lung diseases. Epithelial dysfunction is thought to play a prominent role in disease pathology and we sought to characterize secreted signals that may contribute to disease pathology. Transcriptional profiling of senescent type II alveolar epithelial cells (AEC2s) from mice with epithelial-specific telomere dysfunction identified the TGFß family member, growth and differentiation factor 15 (Gdf15), as the most significantly upregulated secreted protein. Gdf15 expression is induced in response to telomere dysfu...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - August 21, 2019 Category: Cytology Authors: Zhang Y, Jiang M, Nouraie M, Roth MG, Tabib T, Winters S, Chen X, Sembrat J, Chu Y, Cardenes N, Tuder RM, Herzog EL, Ryu C, Rojas M, Lafyatis R, Gibson KF, McDyer JF, Kass DJ, Alder JK Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Defining a pathological role for the vasculature in the development of fibrosis and pulmonary hypertension in interstitial lung disease.
PMID: 31432711 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology)
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - August 21, 2019 Category: Cytology Authors: George PM, Mitchell J Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Cell Fate Analysis in Fetal Mouse Lung Reveals Distinct Pathways for TI and TII Cell Development.
Abstract Alveolar type I (TI) cells are large squamous cells that cover>95% of the internal surface area of the lung; type II (TII) cells are small cuboidal cells with distinctive intracellular surfactant storage organelles. Based on autoradiographic studies in the 1970s, the long-held paradigm of alveolar epithelial development has been a linear progression from undifferentiated progenitor cells through TII cells to TI cells. Subsequent data support the existence of more complex pathways. Recently, a bipotent TI/TII progenitor cell at E18 has been inferred both from marker expression in developing airways and ...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - August 21, 2019 Category: Cytology Authors: Gonzalez R, Leaffer D, Chapin C, Gillespie A, Eckalbar W, Dobbs LG Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Integrating multi-omics longitudinal data to reconstruct networks underlying lung development.
Abstract A comprehensive understanding of the dynamic regulatory networks that govern postnatal alveolar lung development is still lacking. To construct such a model, we profiled mRNA, microRNA, DNA methylation, and proteomics of developing murine alveoli isolated by laser capture microdissection at 14 predetermined time points. We developed a detailed comprehensive and interactive model that provides information about the major expression trajectories, the regulators of specific key events, and the impact of epigenetic changes. Intersecting the model with single cell RNAseq (scRNA-Seq) data led to the identificat...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - August 21, 2019 Category: Cytology Authors: Ding J, Ahangari F, Espinoza CR, Chhabra D, Nicola T, Yan X, Lal CV, Hagood JS, Kaminski N, Bar-Joseph Z, Ambalavanan N Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Sulfatide-activated type II NKT cells suppress immunogenic maturation of lung dendritic cells in murine models of asthma.
Abstract Our previous study showed that sulfatide-activated type II natural killer T (NKT) cells can prevent allergic airway inflammation in an OVA-induced murine model of asthma, but the underline mechanism is unclear. Recently, sulfatide-activated type II NKT cells were shown to modulate the function of dendritic cells (DCs) in experimental autoimmune encephalomyelitis (EAE) and non-obese diabetic (NOD). Thus, it was hypothezied that sulfatide-activated type II NKT cells may modulate the function of lung dendritic cells (LDCs) in asthmatic mice. Our data showed that, in our mouse models, activation of type II NK...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - August 21, 2019 Category: Cytology Authors: Zhang G, Pan H, Nie H, Li S, He S, Yang J Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Mitochondrial DNA Variation Modulates Alveolar Development in Newborn Mice Exposed to Hyperoxia.
CONCLUSIONS: Our study suggests that neonatal C57 mtDNA carrying strains have increased hyperoxia-induced hypoalveolarization, pulmonary mechanical dysfunction and mitochondrial bioenergetic and redox dysfunction vs. C3H mtDNA strains. Therefore, mtDNA haplogroup variation-induced differences in mitochondrial function could modify neonatal alveolar development and BPD susceptibility. PMID: 31432715 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology)
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - August 21, 2019 Category: Cytology Authors: Kandasamy J, Rezonzew G, Jilling T, Ballinger SW, Ambalavanan N Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Moderate hyperoxia induces senescence in developing human lung fibroblasts.
Abstract Hyperoxia exposure in premature infants increases the risk of subsequent lung diseases such as asthma and bronchopulmonary dysplasia. Fibroblasts help maintain bronchial and alveolar integrity. Thus understanding mechanisms by which hyperoxia influences fibroblasts is critical. Cellular senescence is increasingly recognized as important to pathophysiology of multiple diseases. We hypothesized that clinically-relevant moderate hyperoxia (
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - August 14, 2019 Category: Cytology Authors: You K, Parikh P, Khandalavala K, Wicher S, Manlove LJ, Yang B, Roesler AM, Roos B, Teske JJ, Britt RD, Pabelick CM, Prakash YS Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Surfactant Protein-D Modulation of Pulmonary Macrophage Phenotype is Controlled by S-Nitrosylation.
Abstract Surfactant protein-D (SP-D), a regulator of pulmonary innate immunity, whose oligomeric state can be altered through S-nitrosylation to regulate its signaling function in macrophages. Here, we examined how nitrosylation of SP-D alters the phenotypic response of macrophages to stimuli, both in vivo and in vitro. Bronchoalveolar lavage (BAL) from C57/Bl6 and SP-D overexpressing (SP-D OE) mice was incubated with RAW264.7 cells ± LPS. LPS induces expression of inflammatory genes, IL1B and NOS2, which is reduced 10-fold by SP-D OE-BAL. S-nitrosylation of the SP-D OE-BAL (SNO-SP-D OE-BAL) abrogated this ...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - August 14, 2019 Category: Cytology Authors: Guo C, Atochina-Vasserman EN, Abramova E, Smith LC, Beers MF, Gow AJ Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Role of TRPP2 in mouse airway smooth muscle tension and respiration.
Abstract Polycystin-2 (TRPP2) is encoded by the Pkd2 gene, and mutation of this gene can cause autosomal dominant polycystic kidney disease (ADPKD). Some patients with ADPKD experience extrarenal manifestations, including radiologic and clinical bronchiectasis. We hypothesized that TRPP2 may regulate airway smooth muscle (ASM) tension. Thus, we used smooth muscle-Pkd2 conditional knockout (Pkd2SM-CKO) mice to investigate whether TRPP2 regulated ASM tension and whether TRPP2 deficiency contributed to bronchiectasis associated with ADPKD. Compared with wild-type mice, Pkd2SM-CKO mice breathed shallower and faster, a...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - August 14, 2019 Category: Cytology Authors: Sang D, Bai S, Yin S, Jiang S, Ye L, Hou W, Yao Y, Wang H, Shen Y, Shen B, Du J Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Microrna-221 is overexpressed in the equine asthmatic airway smooth muscle and modulates smooth muscle cell proliferation.
In conclusion, we demonstrate for the first time an upregulation of miR-221 in asthmatic airway smooth muscle and confirm the involvement of miR-221 in ASM cell proliferation by regulation of the cell cycle arrest genes. Targeting miR-221 network genes may represent novel approach for the treatment of ASM remodeling in asthma. PMID: 31389734 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology)
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - August 7, 2019 Category: Cytology Authors: Issouf M, Vargas A, Boivin R, Lavoie JP Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Potential Role of Cartilage Oligomeric Matrix Protein in the Modulation of Pulmonary Arterial Smooth Muscle Superoxide by Hypoxia.
Abstract Changes in reactive oxygen species and extracellular matrix seem to participate in pulmonary hypertension development. Since we recently reported evidence for chronic hypoxia decreasing expression of cartilage oligomeric matrix protein (COMP) and evidence for this controlling loss of pulmonary arterial smooth muscle BMP receptor-2 (BMPR2) and contractile phenotype proteins, we examined if changes in superoxide metabolism could be an important factor in a bovine pulmonary artery (BPA), organoid cultured under hypoxia for 48hrs model. Hypoxia (3% oxygen) caused a depletion of COMP in BPA, but not in bovine ...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - August 7, 2019 Category: Cytology Authors: Yu H, Alruwaili N, Hu B, Kelly MR, Zhang B, Sun D, Wolin MS Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Endotracheal Tube Mucus as a Source of Airway Mucus for Rheological Study.
Abstract Muco-obstructive lung diseases (MOLDs), like cystic fibrosis and chronic obstructive pulmonary disease, affect a spectrum of subjects globally. In MOLDs, the airway mucus becomes hyperconcentrated, increasing osmotic and viscoelastic moduli and impairing mucus clearance. MOLD research requires relevant sources of healthy airway mucus for experimental manipulation and analysis. Mucus collected from endotracheal tubes (ETT) may represent such a source with benefits, e.g., in vivo production, over canonical sample types such as sputum or human bronchial epithelial (HBE) mucus. Ionic and biochemical compositi...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - August 7, 2019 Category: Cytology Authors: Markovetz MR, Subramani DB, Kissner WJ, Morrison CB, Garbarine IC, Ghio AL, Ramsey KA, Arora H, Kumar PA, Nix DB, Kumagai T, Krunkosky TM, Krause DC, Radicioni G, Alexis NE, Kesimer M, Tiemeyer M, Boucher RC, Ehre C, Hill DB Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Corrigendum.
CORRIGENDUM. Am J Physiol Lung Cell Mol Physiol. 2019 Aug 01;317(2):L303 Authors: PMID: 31386817 [PubMed] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology)
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - August 1, 2019 Category: Cytology Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Chemokine signaling axis between endothelial and myeloid cells regulates development of pulmonary hypertension associated with pulmonary fibrosis and hypoxia.
Abstract Pulmonary hypertension complicates the care of many patients with chronic lung diseases (defined as Group 3 pulmonary hypertension), yet the mechanisms that mediate the development of pulmonary vascular disease are not clearly defined. Despite being the most prevalent form of pulmonary hypertension, to date there is no approved treatment for patients with disease. Myeloid-derived suppressor cells (MDSC) and endothelial cells in the lung express the chemokine receptor CXCR2, implicated in the evolution of both neoplastic and pulmonary vascular remodeling. However, precise cellular contribution to lung dise...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - July 31, 2019 Category: Cytology Authors: Oliveira AC, Fu C, Lu Y, Williams MA, Pi L, Brantly ML, Ventetuolo CE, Raizada MK, Mehrad B, Scott EW, Bryant AJ Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Pulmonary inflammation induced by low dose particulate matter exposure in mice.
In conclusion, a sub-chronic low level exposure to PM can have an adverse effect on lung health, which should be taken into consideration for the planning of roads and residential buildings. PMID: 31364371 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology)
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - July 31, 2019 Category: Cytology Authors: Chan YL, Wang B, Chen H, Ho KF, Cao J, Hai G, Jalaludin B, Herbert C, Thomas PS, Saad S, Oliver BG Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Allele-specific expression identified rs2509956 as a novel long-distance cis-regulatory SNP for SCGB1A1, an important gene for multiple pulmonary diseases.
Abstract SCGB1A1 (secretoglobin family 1A member 1) is an important protein for multiple pulmonary diseases, especially asthma, chronic obstructive pulmonary disease and lung cancer. One SNP at 5' untranslated region of SCGB1A1, rs3741240, had been suggested to be associated with reduced protein expression and further asthma susceptibility. However, it was still unclear whether there were other cis-regulatory elements for SCGB1A1, which might further contribute to pulmonary diseases. Allele-specific expression (ASE) is a novel approach to identify the functional region in human genome. In the present study, we mea...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - July 19, 2019 Category: Cytology Authors: Li XX, Peng T, Gao J, Feng JG, Wu DD, Yang T, Zhong L, Fu WP, Sun C Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

NOTCH signaling promotes survival of irradiated basal airway stem cells.
Abstract Radiation-induced lung injury to normal airway epithelium is a frequent side-effect and dose-limiting factor in radiotherapy of tumors in the thoracic cavity. NOTCH signaling plays key roles in self-renewal and differentiation of upper airway basal lung stem cells during development and the NOTCH pathway is frequently deregulated in lung cancer. In preclinical lung cancer models, NOTCH inhibition was shown to improve the radiotherapy response by targeting tumor stem cells but the effects in combination with irradiation on normal lung stem cells are unknown. NOTCH/gamma-secretase inhibitors are potent clin...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - July 19, 2019 Category: Cytology Authors: Giuranno L, Wansleeben C, Iannone R, Arathoon L, Hounjet J, Groot AJ, Vooijs M Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Combination Therapy Improves Vascular Volume in Female Rats with Pulmonary Hypertension.
Abstract Pulmonary arterial hypertension (PAH) is a female predominant disease in which progressive vascular remodeling and vasoconstriction result in right ventricular failure and death. Most PAH patients utilize multiple therapies. In contrast, the majority of preclinical therapeutic studies are performed in male rats with a single novel drug often markedly reversing disease in the model. We sought to differentiate single drug therapy from combination therapy in female rats with severe disease. One week after left pneumonectomy, we induced PH in young female Sprague-Dawley rats with an injection of monocrotaline...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - July 19, 2019 Category: Cytology Authors: Lachant D, Meoli DF, Haight D, Staicu S, Akers S, Glickman S, Ambrosini R, Champion HC, White RJ Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Integration of transcriptomic and proteomic data identifies biological functions in cell populations from human infant lung.
Abstract Systems biology uses computational approaches to integrate diverse data types to understand cell and organ behavior. Data derived from complementary technologies, for example transcriptomic and proteomic analyses, are providing new insights into development and disease. We compared mRNA and protein profiles from purified endothelial, epithelial, immune, and mesenchymal cells from normal human infant lung tissue. Signatures for each cell type were identified and compared at both mRNA and protein levels. Cell specific biological processes and pathways were predicted by analysis of concordant and discordant ...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - July 3, 2019 Category: Cytology Authors: Du Y, Clair GC, Al Alam D, Danopoulos S, Schnell D, Kitzmiller JA, Misra RS, Bhattacharya S, Warburton D, Mariani TJ, Pryhuber GS, Whitsett JA, Ansong C, Xu Y Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Histone Deacetylase 6 Regulates Endothelial MyD88-dependent canonical TLR signaling, Lung inflammation, and Alveolar Remodeling in the developing lung.
Abstract Lung endothelial cell (EC) immune activation during bacterial sepsis contributes to acute lung injury and bronchopulmonary dysplasia in premature infants. The epigenetic regulators of sepsis-induced endothelial immune activation, lung inflammation and alveolar remodeling remain unclear. Herein, we examined the role of the cytoplasmic histone deacetylase, HDAC6, in regulating EC Toll-Like Receptor 4 (TLR4) signaling and modulating sepsis-induced lung injury in a neonatal model of sterile sepsis. In human primary microvascular endothelial cells (HPMEC), lipopolysaccharide (LPS)-induced MAPK, IKK-β, and...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - July 3, 2019 Category: Cytology Authors: Menden H, Xia S, Mabry S, Noel-MacDonnell J, Rajasingh J, Qing Ye S, Sampath V Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Inhibition of retinoic acid signaling induces aberrant pericyte coverage and differentiation resulting in vascular defects in congenital diaphragmatic hernia.
Abstract The mortality and morbidity of patients with congenital diaphragmatic hernia (CDH) is primarily caused by treatment-resistant, persistent pulmonary hypertension. Structural vascular changes, exemplified by extensive muscularization, are already present early in gestation, but the origin of these abnormalities is unknown. Understanding the origin of the vascular defects is important to improve treatment modalities. Here, we show that the distribution of pericytes is different and may thereby potentially initiate the vascular pathology in CDH. Transient inhibition of retinoic acid signaling early during pre...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - July 3, 2019 Category: Cytology Authors: Kool HM, Burgisser PE, Edel GG, De Kleer I, Boerema-de Munck A, de Laat I, Chrifi I, Cheng C, van Cappellen WA, Kremers GJ, Tibboel D, Rottier RJ Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Loss of cells expressing Fibroblast Activation Protein (FAP) has variable effects in models of TGF- β and chronic bleomycin-induced fibrosis.
Loss of cells expressing Fibroblast Activation Protein (FAP) has variable effects in models of TGF-β and chronic bleomycin-induced fibrosis. Am J Physiol Lung Cell Mol Physiol. 2019 Jun 12;: Authors: Kimura T, Monslow J, Klampatsa A, Leibowitz M, Sun J, Liousia M, Woodruff P, Moon E, Todd L, Pure E, Albelda SM Abstract Fibroblast activation protein (FAP), a cell surface serine protease, is up-regulated on a subset of activated fibroblasts (often distinct from a-smooth muscle actin-expressing myofibroblasts) associated with matrix remodeling, including fibroblasts in idiopathic pulmonary fibrosis....
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - June 12, 2019 Category: Cytology Authors: Kimura T, Monslow J, Klampatsa A, Leibowitz M, Sun J, Liousia M, Woodruff P, Moon E, Todd L, Pure E, Albelda SM Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Therapeutic Effects of Soluble Guanylate Cyclase (sGC) Stimulation on Pulmonary Hemodynamics and Emphysema in Guinea Pigs Chronically Exposed to Cigarette Smoke.
In conclusion, in guinea pigs chronically exposed to CS, sGC stimulation exerts beneficial effects on the lung parenchyma and the pulmonary vasculature, suggesting that sGC stimulators might be a potential alternative for COPD treatment that deserves further evaluation. PMID: 31166128 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology)
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - June 5, 2019 Category: Cytology Authors: Paul T, Blanco I, Aguilar D, Tura-Ceide O, Bonjoch C, Smolders VF, Peinado VI, Barberà JA Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Cigarette and ENDS preparations differentially regulate ion channels and mucociliary clearance in primary normal human bronchial 3D cultures.
This study aimed to compare the effects of acute exposure of primary normal human bronchial epithelial (NHBE) 3D cultures at air-liquid interface to combustible cigarette and ENDS preparations on mucociliary function including ion channel function, ciliary beat frequency (CBF) and airway surface liquid (ASL) height. Differentiated NHBE cultures were exposed to whole smoke conditioned media (WS-CM) or total particulate matter (TPM) prepared from 3R4F reference cigarettes, whole aerosol conditioned media (ACM) or e-TPM generated from a marketed ENDS product, or nicotine alone. We found that a dose of 7µg/ml equi-nicoti...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - June 5, 2019 Category: Cytology Authors: Rayner RE, Makena P, Prasad GL, Cormet-Boyaka E Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Transitional human alveolar type II epithelial cells suppress extracellular matrix and growth factor gene expression in lung fibroblasts.
Abstract Epithelial-fibroblast interactions are thought to be very important in adult lung remodeling and fibrosis, but the specifics of these interactions are not well defined. We developed co-culture systems to define the effects of adult human alveolar epithelial cells on lung fibroblasts. Alveolar type II cells cultured on floating collagen gels reduced the expression of type 1 collagen (COL1A1) and alpha smooth muscle actin (ACTA2) in fibroblasts. They also reduced fibroblast expression of hepatocyte growth factor (HGF), fibroblast growth factor 7 (FGF7, KGF), and FGF10. When type II cells were cultured at an...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - June 5, 2019 Category: Cytology Authors: Correll KA, Edeen KE, Zemans RL, Redente EF, Serban KA, Curran-Everett D, Edelman BL, Mikels-Vigdal A, Mason RJ Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

The Huxley crossbridge model as the basic mechanism for airway smooth muscle contraction.
ano P Abstract The cyclic interaction between myosin crossbridges and actin filaments underlies smooth muscle contraction. Phosphorylation of the 20-kDa myosin light chain (MLC20) is a crucial step in activating the crossbridge cycle. Our current understanding of smooth muscle contraction is based on observed correlations among MLC20 phosphorylation, maximal shortening velocity (Vmax), and isometric force over the time course of contraction. However during contraction there are changes in the extent of phosphorylation of many additional proteins as well as changes in activation of enzymes associated with the signa...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - May 22, 2019 Category: Cytology Authors: Luo L, Wang L, Paré PD, Seow CY, Chitano P Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Organic dust, causing both oxidative stress and Nrf2 activation, is phagocytized by bronchial epithelial cells.
CONCLUSIONS: Bronchial epithelial cells become phagocytic in response to OD exposure, resulting in an increase in endogenous oxidative stress. Nrf2-dependent mechanisms mediate the antioxidant response to OD. PMID: 31116579 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology)
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - May 22, 2019 Category: Cytology Authors: McGovern TK, Farahnak S, Chen M, Larsson K, Martin JG, Adner M Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Autophagy proteins are required for club cell structure and function in airways.
Abstract Epithelial cells that line lung airways produce and secrete proteins with important roles in barrier function and host defense. Secretion of airway goblet cells is controlled by autophagy proteins during inflammatory conditions, resulting in accumulation of mucin proteins. We hypothesized that autophagy proteins would also be important in the function of club cells, a dominant secretory airway epithelial cell that is dysregulated in chronic lung disease. We found that in the absence of an inflammatory stimulus, mice with club cells deficient for the autophagy protein Atg5, had a markedly diminished expres...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - May 22, 2019 Category: Cytology Authors: Malvin NP, Kern JT, Liu TC, Brody SL, Stappenbeck T Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Cyclic compression increases F508 Del CFTR expression in ciliated human airway epithelium.
Abstract Mechanisms by which transepithelial pressure changes observed during exercise and airway clearance can benefit lung health are challenging to study. Here, we have studied 117 mature, fully ciliated airway epithelial cell filters grown at air liquid interface grown from 10 cystic fibrosis (CF) and 19 control subjects. These were exposed to cyclic increases in apical air pressure of 15 cm H2O for varying times. We measured the effect on proteins relevant to lung health, with a focus on the CF transmembrane regulator (CFTR). Immunoflourescence and immunoblot data were concordant in demonstrating that air pre...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - May 22, 2019 Category: Cytology Authors: Marozkina N, Bosch J, Cotton CU, Smith L, Seckler JV, Zaman K, Rehman S, Periasamy A, Gaston H, Altawallbeh G, Davis M, Jones DR, Schilz R, Randell SH, Gaston B Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

In utero tobacco smoke exposure alters lung inflammation, viral clearance and CD8+ T cell responses in neonatal mice infected with respiratory syncytial virus.
Abstract Maternal smoking during pregnancy and exposure of infants to cigarette smoke is strongly associated with adverse health effects in childhood including higher susceptibility to respiratory viral infections. Human respiratory syncytial virus (HRSV) is the most important cause of lower respiratory tract infection among young infants. Exacerbation of respiratory disease, including HRSV-bronchiolitis and higher susceptibility to HRSV infection is well-correlated with previous smoke exposure. The mechanisms of recurrence and susceptibility to viral pathogens after passive smoke exposure are multifactorial and i...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - May 15, 2019 Category: Cytology Authors: Cheemarla NR, Uche IK, McBride K, Naidu S, Guerrero-Plata A Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Role of phospholipase D in bleomycin-induced mitochondrial reactive oxygen species generation, mitochondrial DNA damage and pulmonary fibrosis.
In this study, we have identified phospholipase D (PLD) generated phosphatidic acid (PA) signaling in the development of pulmonary fibrosis (PF). Of the PLD isoenzymes, the protein expression of PLD2, but not PLD1, was up-regulated in lung tissues from IPF patients and bleomycin challenged mice. Both PLD1 (Pld1-/-) and PLD2 (Pld2-/-) deficient mice were protected against bleomycin induced lung inflammation and fibrosis, thereby establishing the role of PLD in fibrogenesis. The role of PLD1 and PLD2 in bleomycin-induced lung epithelial injury was investigated by infecting bronchial airway epithelial cells (Beas2B) with cata...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - May 15, 2019 Category: Cytology Authors: Suryadevara V, Huang L, Kim SJ, Cheresh S, Shaaya M, Bandela M, Fu P, Feghali-Bostwick CA, Di Paolo G, Kamp DW, Natarajan V Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Cardiac glycosides decrease influenza virus replication by inhibiting cell protein translational machinery.
Abstract Cardiac glycosides (CG) are used primarily for cardiac failure and have been reported to have other effects, including inhibition of viral replication. Here we set out to study mechanisms by which CG as inhibitors of the Na,K-ATPase, decrease influenza A virus (IAV) replication in the lungs. We found that CG inhibit influenza virus replication in alveolar epithelial cells by decreasing intracellular potassium which in turn inhibits protein translation, independently of viral entry, mRNA transcription, and protein degradation. These effects were independent of the Src signaling pathway and intracellular ca...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - March 20, 2019 Category: Cytology Authors: Amarelle L, Katzen J, Shigemura M, Welch LC, Cajigas H, Peteranderl C, Celli D, Herold S, Lecuona E, Sznajder JI Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Lung growth after pneumonectomy: searching for the right stimuli.
PMID: 30892075 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology)
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - March 20, 2019 Category: Cytology Authors: Ochs M Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Extracellular Vesicles in Lung Health, Disease, and Therapy: Mini-Review and Special Call for papers.
Abstract Both physiological homeostasis and pathological disease processes in the lung typically result from complex, yet coordinated multicellular responses which are synchronized via paracrine and endocrine intercellular communication pathways. Of late, extracellular vesicles have emerged as important information shuttles that can coordinate and disseminate homeostatic and disease signals. In parallel, extracellular vesicles in biological fluids such as sputum, mucus, epithelial lining fluid, edema fluid, the pulmonary circulation, pleural fluid, and lymphatics have emerged as promising candidate biomarkers for ...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - March 20, 2019 Category: Cytology Authors: McVey MJ, Maishan M, Blokland KEC, Bartlett N, Kuebler WM Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Prophylactic treatment with MSC derived exosomes attenuates traumatic acute lung injury in rats.
In conclusion, the results provide evidence that miR-124-3p transferred by MSCs-derived exosomes inhibited P2X7 expression, thus improving OS injury and suppressing inflammatory response in traumatic ALI, highlighting a potential pretreatment for traumatic ALI. PMID: 30892077 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology)
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - March 20, 2019 Category: Cytology Authors: Li QC, Liang Y, Su ZB Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Vascular TSP1-CD47 Signaling Promotes Sickle Cell-Associated Arterial Vasculopathy and Pulmonary Hypertension in Mice.
Abstract Pulmonary hypertension (PH) is a leading cause of death in sickle cell disease (SCD). Hemolysis and oxidative stress are contributing factors to SCD-associated PH. We have reported that the protein thrombospondin-1 (TSP1) is elevated in the plasma of patients with SCD and by interacting with its receptor CD47 limits vasodilation of distal pulmonary arteries ex vivo. We hypothesized that the TSP1-CD47 interaction may promote PH in SCD. We found that TSP1 and CD47 are upregulated in the lungs of BERK sickle mice and patients with SCD-associated PH. We then generated chimeric animals by transplanting BERK bo...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - March 20, 2019 Category: Cytology Authors: Novelli EM, Little-Ihrig L, Knupp HE, Rogers NM, Yao M, Baust JJ, Meijles D, St Croix CM, Ross MA, Pagano PJ, DeVallance ER, Miles G, Potoka KP, Isenberg JS, Gladwin MT Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Senescence in the Lung: Is This Getting Old?
PMID: 30892079 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology)
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - March 20, 2019 Category: Cytology Authors: Morty RE, Prakash YS Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Activation of mTORC1/PGC1 axis promotes mitochondrial biogenesis and induces cellular senescence in the lung epithelium.
In this study, we uncovered that the mitochondrial biogenesis pathway driven by the mTOR/PGC1α/β axis is markedly upregulated in senescent lung epithelial cells. Using two different models, we show that activation of this pathway associates with other features characteristic of enhanced mitochondrial biogenesis, including elevated number of mitochondrion per cell, increased oxidative phosphorylation and augmented mitochondrial ROS production. Furthermore, we found that pharmacological inhibition of the mTORC1 complex with rapamycin not only restored mitochondrial homeostasis but also reduced cellular senescence ...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - March 20, 2019 Category: Cytology Authors: Summer R, Shaghaghi H, Schriner D, Roque W, Sales D, Cuevas-Mora K, Desai V, Bhushan A, Ramirez MI, Romero F Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Acetyl-CoA carboxylase inhibition regulates microtubule dynamics and intracellular transport in cystic fibrosis epithelial cells.
Abstract The use of high-dose ibuprofen as an anti-inflammatory therapy in cystic fibrosis has been shown to be an effective intervention though use is limited due to potential adverse events. Identifying the mechanism of ibuprofen efficacy would aid in the development of new therapies that avoid these adverse events. Previous findings demonstrated that ibuprofen treatment restores the regulation of microtubule dynamics in cystic fibrosis (CF) epithelial cells through a 5' adenosine monophosphate-activated protein kinase (AMPK)-dependent mechanism. The goal of this study is to define the AMPK pathway that leads to...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - March 20, 2019 Category: Cytology Authors: Rymut SM, Lu B, Perez A, Corey DA, Lamb K, Cotton CU, Kelley TJ Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

MLN4924 protects against interleukin-17A-induced pulmonary inflammation by disrupting ACT1-mediated signaling.
Abstract An excessive inflammatory response in terminal airways, alveoli, and the lung interstitium eventually leads to pulmonary hypertension and chronic obstructive pulmonary disease. Proinflammatory cytokine interleukin-17A (IL-17A) has been implicated in the pathogenesis of pulmonary inflammatory diseases. MLN4924, an inhibitor of NEDD8-activating enzyme (NAE), is associated with the treatment of various types of cancers, but its role in the IL-17A-mediated inflammatory response has not been identified. Here, we report that MLN4924 can markedly reduce the expression of proinflammatory cytokines and chemokines ...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - March 20, 2019 Category: Cytology Authors: Hao R, Song Y, Li R, Wu Y, Yang X, Li X, Qian F, Ye RD, Sun L Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Extracellular Vesicles in Pulmonary Hypertension: Lessons from Mesenchymal Stromal Cell-Derived Exosomes.
PMID: 30864818 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology)
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - March 13, 2019 Category: Cytology Authors: Hewes JL, Bauer NN Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Early Studies of Airway Submucosal Glands.
This article provides a comprehensive review of early research on the structure and function of airway submucosal glands. The literature before 1950, or so, is virtually unknown, but in addition to being of historical interest, it contains much of relevance to current research. Airway glands were first mentioned in 1602. The first description of their general form, size and distribution was in 1712. Gland morphology was determined in 1827 by injecting mercury into their openings. Wax was later used. Detailed comparative information for all regions of the tracheobronchial tree was provided by Frankenhauser in 1879. Histolog...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - March 13, 2019 Category: Cytology Authors: Widdicombe JH Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Surfactant plus budesonide decreases lung and systemic inflammation in mechanically ventilated preterm sheep.
CONCLUSION: In ventilated preterm lambs, most of the budesonide left the lung within 24 h. The addition of budesonide to surfactant improved physiology, decreased markers of lung injury, and decreased systemic responses in liver and brain. PMID: 30838863 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology)
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - March 6, 2019 Category: Cytology Authors: Kothe TB, Kemp MW, Schmidt AF, Royse E, Salomone F, Clarke MW, Musk GC, Jobe AH, Hillman NH Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Embryonic Mesothelium in Motion: A Systematic Study.
PMID: 30838864 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology)
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - March 6, 2019 Category: Cytology Authors: El Agha E Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Loss of myeloid-specific protein phosphatase 2A enhances lung injury and fibrosis and results in IL-10 dependent sensitization of epithelial cell apoptosis.
Abstract Protein phosphatase 2A (PP2A), a ubiquitously expressed ser/thr phosphatase is an important regulator of cytokine signaling and cell function. We previously showed that myeloid-specific deletion of PP2A (LysMcrePP2A-/-) increased mortality in a murine peritoneal sepsis model. In the current study, we assessed the role of myeloid PP2A in regulation of lung injury induced by lipopolysaccharide (LPS) or bleomycin delivered intratracheally. LysMcrePP2A-/- mice experienced increased lung injury in response to both LPS and bleomycin. LysMcrePP2A-/- mice developed more exuberant fibrosis in response to bleomycin...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - March 6, 2019 Category: Cytology Authors: Sun L, Hult EM, Cornell TT, Kim KK, Shanley TP, Wilke CA, Agarwal M, Gurcynski SJ, Moore BB, Dahmer MK Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research