TMEM16A Mediated Mucus Production in Human Airway Epithelial Cells.
We examined this question using BCi-NS1 cells, a human airway basal cell line that maintains multipotent differentiation capacity, and the two human airway epithelial cell lines, Calu-3 and CFBE. The data demonstrate that exposure of airway epithelial cells to IL-8 and IL-13, two cytokines known to be enhanced in CF and asthma, respectively, leads to increase in mucus production. Expression of MUC5AC was fully dependent on expression of TMEM16A, as shown by siRNA-knockdown of TMEM16A. In addition, different inhibitors of TMEM16A attenuated IL-13 induced mucus production. Interestingly, in CFBE cells expressing F508delCFTR,...
Source: American Journal of Respiratory Cell and Molecular Biology - October 7, 2020 Category: Molecular Biology Authors: Cabrita I, Benedetto R, Wanitchakool P, Lerias J, Centeio R, Ousingsawat J, Schreiber R, Kunzelmann K Tags: Am J Respir Cell Mol Biol Source Type: research

Lung Expression of Human ACE2 Sensitizes the Mouse to SARS-CoV-2 Infection.
This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). PMID: 32991819 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - September 28, 2020 Category: Molecular Biology Authors: Han K, Blair RV, Iwanaga N, Liu F, Russell-Lodrigue KE, Qin Z, Midkiff CC, Golden NA, Doyle-Meyers LA, Kabir ME, Chandler KE, Cutrera KL, Ren M, Monjure CJ, Lehmicke G, Fischer T, Beddingfield B, Wanek AG, Birnbaum A, Maness NJ, Roy CJ, Datta PK, Rappapor Tags: Am J Respir Cell Mol Biol Source Type: research

Immune Modulation to Improve Survival of Viral Pneumonia in Mice.
CONCLUSIONS: Stimulation of local innate immunity within the lungs by TLR agonists early in disease or suppression of adaptive immunity by systemic CD8+ T cell depletion late in disease improves outcomes of viral pneumonia in mice. These data reveal opportunities for targeted immunomodulation to protect susceptible human subjects. PMID: 32853024 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - August 26, 2020 Category: Molecular Biology Authors: Wali S, Flores JR, Jaramillo AM, Goldblatt DL, Pantaleón García J, Tuvim MJ, Dickey BF, Evans SE Tags: Am J Respir Cell Mol Biol Source Type: research

Prenatal Exposure to E-Cigarette Aerosols Leads to Sex-dependent Pulmonary Extracellular Matrix Remodeling and Myogenesis in Offspring Mice.
Abstract Electronic cigarette (e-cig) vaping is a serious concern, since many pregnant women who vape consider it safe. However, little is known about the harmful effects of prenatal e-cig exposure on the adult offspring, especially on extracellular matrix (ECM) deposition and myogenesis in the lungs of offspring. We evaluated the biochemical and molecular implications of maternal exposure during pregnancy to e-cigs on the adult offspring of both sexes with a particular focus on pulmonary ECM remodeling and myogenesis. Pregnant CD-1 mice were exposed to e-cig aerosol with or without nicotine, throughout gestation,...
Source: American Journal of Respiratory Cell and Molecular Biology - August 26, 2020 Category: Molecular Biology Authors: Wang Q, Sundar IK, Blum JL, Ratner JR, Lucas JH, Chuang TD, Wang Y, Liu J, Rehan VK, Zelikoff JT, Rahman I Tags: Am J Respir Cell Mol Biol Source Type: research

Dendritic Cells in Pulmonary Hypertension: Foot Soldiers or Hidden Enemies?
PMID: 32804536 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - August 16, 2020 Category: Molecular Biology Authors: Guignabert C Tags: Am J Respir Cell Mol Biol Source Type: research

Application of Proteomics in Sarcoidosis.
Abstract Sarcoidosis is a multisystem disease with heterogeneity in manifestations and outcomes. System-level studies leveraging "omics" technologies are expected to define mechanisms contributing to sarcoidosis heterogeneous manifestations and course. With improvements in mass spectrometry (MS) and bioinformatics, it is possible to study protein abundance for a large number of proteins simultaneously. Contemporary fast-scanning MS enables acquisition of spectral data for deep coverage of the proteins with data-dependent acquisition-MS or data-independent acquisition-MS modes. Studies leveraging MS-based...
Source: American Journal of Respiratory Cell and Molecular Biology - August 16, 2020 Category: Molecular Biology Authors: Guerrero CR, Maier LA, Griffin TJ, Higgins L, Najt CP, Perlman DM, Bhargava M Tags: Am J Respir Cell Mol Biol Source Type: research

Single Nucleus RNASeq Profiling of Mouse Lung: Reduced Dissociation Bias and Improved Rare Cell Type Detection Compared with Single Cell RNASeq.
We present a snRNASeq protocol and compare its results with scRNA-seq. Two nuclear suspensions were prepared in lysis buffer on ice while one cell suspension was generated using enzymatic and mechanical dissociation. Cells and nuclei were processed using the 10x Genomics platform, and sequencing data analyzed by Seurat. 16,110 single nucleus and 11,934 single cell transcriptomes were generated. Gene detection rates were equivalent in snRNASeq and scRNASeq (~1,700 genes and 3,000 UMI per cell) when mapping intronic and exonic reads. In the combined data, 89% of epithelial cells were identified by snRNASeq, versus 22.2% of i...
Source: American Journal of Respiratory Cell and Molecular Biology - August 16, 2020 Category: Molecular Biology Authors: Koenitzer JR, Wu H, Atkinson JJ, Brody SL, Humphreys BD Tags: Am J Respir Cell Mol Biol Source Type: research

Heart of the Matter: Divergent Roles of HIFs in Hypoxia-induced RV Hypertrophy.
PMID: 32790477 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - August 12, 2020 Category: Molecular Biology Authors: Nozik-Grayck E, Shimoda LA Tags: Am J Respir Cell Mol Biol Source Type: research

Will Intranasal Leptin Mitigate Opioid-Induced Sleep Disordered Breathing?
PMID: 32790505 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - August 12, 2020 Category: Molecular Biology Authors: Prasad B, Chowdhuri S Tags: Am J Respir Cell Mol Biol Source Type: research

The Proinflammatory Activity of Structurally Altered Elastic Fibers.
Abstract The mechanisms responsible for the increased loss of pulmonary function following acute lung inflammation in COPD remain poorly understood. To investigate this process, our laboratory developed a hamster model that employs a single intratracheal (IT) instillation of lipopolysaccharide (LPS) to superimpose an inflammatory response on lungs treated with IT elastase one week earlier. Parameters measured at 2 days post-LPS included total leukocyte content and percent neutrophils in bronchoalveolar lavage fluid (BALF), and BALF levels of both total and peptide-free elastin-specific crosslinks, desmosine and is...
Source: American Journal of Respiratory Cell and Molecular Biology - August 12, 2020 Category: Molecular Biology Authors: Mehraban S, Gu G, Ma S, Liu X, Turino G, Cantor J Tags: Am J Respir Cell Mol Biol Source Type: research

PV1: Gatekeeper of Endothelial Permeability.
PMID: 32780962 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - August 10, 2020 Category: Molecular Biology Authors: Zhao Y, Zhao J Tags: Am J Respir Cell Mol Biol Source Type: research

Extracellular Vesicles: Bidirectional Accelerators of Cellular Senescence in Fibrosis?
PMID: 32780980 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - August 10, 2020 Category: Molecular Biology Authors: Goliwas KF, Deshane JS Tags: Am J Respir Cell Mol Biol Source Type: research

DNGR1-Cre-mediated Deletion of Tnfaip3/A20 in Conventional Dendritic Cells Induces Pulmonary Hypertension in Mice.
Abstract Chronic perivascular inflammation is a prominent feature in the lungs of idiopathic pulmonary arterial hypertension (IPAH). Although the proportions of conventional dendritic cells (cDCs) and plasmacytoid DCs are increased in IPAH lungs, it remains unknown whether activated cDCs play a pathogenic role. The Tnfaip3 gene encodes the ubiquitin-binding protein A20, which is a negative regulator of NF-κB, critically involved in DC activation. Targeting of Tnfaip3/A20 in cDCs was achieved by Clec9a (DNGR1)-Cre-mediated excision of the Tnfaip3 gene in Tnfaip3DNGR1-KO mice. Mice were evaluated for signs of ...
Source: American Journal of Respiratory Cell and Molecular Biology - August 4, 2020 Category: Molecular Biology Authors: Koudstaal T, van Hulst JAC, Das T, Neys SFH, Merkus D, Bergen IM, de Raaf MA, Bogaard HJ, Boon L, van Loo G, Aerts JGJV, Boomars KA, Kool M, Hendriks RW Tags: Am J Respir Cell Mol Biol Source Type: research

Extracellular Vesicles from Fibroblasts Induce Epithelial Cell Senescence in Pulmonary Fibrosis.
Abstract Aberrant epithelial-mesenchymal interactions have critical roles in regulating fibrosis development. The involvement of extracellular vesicles (EVs), including exosomes, remains to be elucidated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Here, we found that lung fibroblasts (LFs) from IPF patients induce cellular senescence via EV-mediated transfer of pathogenic cargo to lung epithelial cells. Mechanistically, IPF LF-derived EVs increased mitochondrial reactive oxygen species (mtROS) and associated mitochondrial damage in lung epithelial cells, leading to activation of the DNA damage resp...
Source: American Journal of Respiratory Cell and Molecular Biology - July 29, 2020 Category: Molecular Biology Authors: Kadota T, Yoshioka Y, Fujita Y, Araya J, Minagawa S, Hara H, Miyamoto A, Suzuki S, Fujimori S, Kohno T, Fujii T, Kishi K, Kuwano K, Ochiya T Tags: Am J Respir Cell Mol Biol Source Type: research

Vaping: Cell Damage at the Receiving ENDS.
PMID: 32648766 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - July 9, 2020 Category: Molecular Biology Authors: Knapp S Tags: Am J Respir Cell Mol Biol Source Type: research

Steps Toward Cell Therapy for Cystic Fibrosis.
PMID: 32648785 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - July 9, 2020 Category: Molecular Biology Authors: Koh KD, Erle DJ Tags: Am J Respir Cell Mol Biol Source Type: research

Intranasal Leptin Prevents Opioid Induced Sleep Disordered Breathing in Obese Mice.
Abstract Respiratory depression is the main cause of morbidity and mortality associated with opioids. Obesity increases opioid-related mortality, which is mostly related to co-morbid obstructive sleep apnea. Naloxone, a μ-opioid receptor blocker, is an effective antidote, but it reverses analgesia. Similar to obese humans, diet-induced obese mice hypoventilate during sleep and develop obstructive sleep apnea, which can be treated with intranasal leptin. We hypothesized that intranasal leptin reverses opioid-induced sleep disordered breathing in obese mice without decreasing analgesia. To test this hypothesis, d...
Source: American Journal of Respiratory Cell and Molecular Biology - June 29, 2020 Category: Molecular Biology Authors: Freire C, Pho H, Kim LJ, Wang X, Dyavanapalli J, Streeter SR, Fleury-Curado T, Sennes LU, Mendelowitz D, Polotsky VY Tags: Am J Respir Cell Mol Biol Source Type: research

Metabolomics to Predict Antiviral Drug Efficacy in COVID-19.
PMID: 32574504 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - June 22, 2020 Category: Molecular Biology Authors: Migaud M, Gandotra S, Chand HS, Gillespie MN, Thannickal VJ, Langley RJ Tags: Am J Respir Cell Mol Biol Source Type: research

Assessing Human Airway Epithelial Progenitor Cells for Cystic Fibrosis Cell Therapy.
Abstract Cystic fibrosis (CF) is caused by loss-of-function mutations in the CF transmembrane regulator (CFTR) gene. Pharmacologic therapies directed at CFTR have been developed but are not effective for mutations that result in little or no mRNA or protein expression. Cell therapy is a potential mutation-agnostic approach to treatment. One strategy is to harvest human bronchial epithelial cells (HBECs) for gene addition or genetic correction, followed by expansion and engraftment. This approach will require cells to grow extensively while retaining their ability to reconstitute CFTR activity. We hypothesized that...
Source: American Journal of Respiratory Cell and Molecular Biology - May 20, 2020 Category: Molecular Biology Authors: Lee RE, Miller SM, Mascenik TM, Lewis CA, Dang H, Boggs ZH, Tarran R, Randell SH Tags: Am J Respir Cell Mol Biol Source Type: research

Comments on "Air Space Distension Precedes Spontaneous Fibrotic Remodeling and Impaired Cholesterol Metabolism in the Absence of Surfactant Protein C".
Comments on "Air Space Distension Precedes Spontaneous Fibrotic Remodeling and Impaired Cholesterol Metabolism in the Absence of Surfactant Protein C". Am J Respir Cell Mol Biol. 2020 May 13;: Authors: Lungarella G, Lucattelli M, Cavarra E, De C.o G PMID: 32401537 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - May 12, 2020 Category: Molecular Biology Authors: Lungarella G, Lucattelli M, Cavarra E, De Cunto G Tags: Am J Respir Cell Mol Biol Source Type: research

Reply to 'Comments on "Air Space Distension Precedes Spontaneous Fibrotic Remodeling and Impaired Cholesterol Metabolism in the Absence of Surfactant Protein C"'.
Reply to 'Comments on "Air Space Distension Precedes Spontaneous Fibrotic Remodeling and Impaired Cholesterol Metabolism in the Absence of Surfactant Protein C"'. Am J Respir Cell Mol Biol. 2020 May 13;: Authors: Lopez-Rodriguez E, Ochs M PMID: 32401539 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - May 12, 2020 Category: Molecular Biology Authors: Lopez-Rodriguez E, Ochs M Tags: Am J Respir Cell Mol Biol Source Type: research

N-Glycosylation Regulates Chitinase 3-like-1 and IL-13 Ligand Binding to IL-13 Receptor α2.
N-Glycosylation Regulates Chitinase 3-like-1 and IL-13 Ligand Binding to IL-13 Receptor α2. Am J Respir Cell Mol Biol. 2020 May 13;: Authors: He CH, Lee CG, Ma B, Kamle S, Choi AMK, Elias JA Abstract Chitinase 3-like-1 (Chi3l1) and IL-13 are both ligands of IL-13 receptor α2 (IL-13Rα2). The binding of the former activates MAPK, AKT and Wnt/β-catenin signaling and plays important roles in innate and adaptive immunity, cellular apoptosis, oxidative injury, allergic inflammation, tumor metastasis and wound healing, fibrosis and repair in the lung. In contrast, the latter binding is...
Source: American Journal of Respiratory Cell and Molecular Biology - May 12, 2020 Category: Molecular Biology Authors: He CH, Lee CG, Ma B, Kamle S, Choi AMK, Elias JA Tags: Am J Respir Cell Mol Biol Source Type: research

Impaired Autophagic Activity Contributes to the Pathogenesis of Bronchopulmonary Dysplasia: Evidence from Murine and Baboon Models.
CONCLUSIONS: Basal autophagy is induced during alveolarization and disrupted during progression of nHILI in mice and BPD in baboons. Becn1+/- mice are more susceptible to nHILI suggesting that preservation of autophagic activity may be an effective protective strategy in BPD. PMID: 32374619 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - May 5, 2020 Category: Molecular Biology Authors: Zhang L, Soni S, Hekimoglu E, Berkelhamer S, Çataltepe S Tags: Am J Respir Cell Mol Biol Source Type: research

Novel Therapy of Bicarbonate, Glutathione and Ascorbic Acid Improves Cystic Fibrosis Mucus Transport.
Abstract Defective airway mucus clearance is a defining characteristic of CF lung disease, and improvements to current mucolytic strategies are needed. Novel approaches targeting a range of contributing mechanisms are in various stages of preclinical and clinical development. ARINA-1 is a new, nebulized product comprised of ascorbic acid, glutathione, and bicarbonate. Using micro-optical coherence tomography, we tested the effect of ARINA-1 on central features of mucociliary clearance in F508del/F508del primary human bronchial epithelial cells to assess its potential as a mucoactive therapy in CF. We found that AR...
Source: American Journal of Respiratory Cell and Molecular Biology - May 5, 2020 Category: Molecular Biology Authors: Adewale AT, Falk Libby E, Fu L, Lenzie A, Boitet ER, Birket SE, Petty CF, Johns JD, Mazur M, Tearney GJ, Copeland D, Durham C, Rowe SM Tags: Am J Respir Cell Mol Biol Source Type: research

Fibroblast Growth Factors Inhibitors in Lung Fibrosis: Friends or Foes?
PMID: 32369705 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - May 4, 2020 Category: Molecular Biology Authors: Guzy R Tags: Am J Respir Cell Mol Biol Source Type: research

May Highlights/Papers by Junior Investigators/NIH News.
Authors: PMID: 32356689 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - April 30, 2020 Category: Molecular Biology Tags: Am J Respir Cell Mol Biol Source Type: research

Surfactant Injury in the Early Phase of Severe Meconium Aspiration Syndrome.
CONCLUSIONS: Various alterations of surfactant phospholipids and proteins were detected in the early phase of severe meconium aspiration, due to hydrolysis and inflammation and as a defensive response. This impairs both surfactant structure and function, finally resulting in a reduced lung aeration. These findings support the development of new surfactant protection and anti-inflammatory strategies for severe MAS. PMID: 32348683 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - April 28, 2020 Category: Molecular Biology Authors: Autilio C, Echaide M, Shankar-Aguilera S, Bragado R, Amidani D, Salomone F, Pérez-Gil J, De Luca D Tags: Am J Respir Cell Mol Biol Source Type: research

Blockade of Pan-fibroblast Growth Factor Receptors Mediates Bidirectional Effects in Lung Fibrosis.
Conclusions] These data suggest that the total inhibition of FGFR signaling can suppress lung fibrosis by inhibiting fibroblast activities, although alveolar injury is simultaneously caused. PMID: 32338990 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - April 26, 2020 Category: Molecular Biology Authors: Morizumi S, Sato S, Koyama K, Okazaki H, Chen Y, Goto H, Kagawa K, Ogawa H, Nishimura H, Kawano H, Toyoda Y, Uehara H, Nishioka Y Tags: Am J Respir Cell Mol Biol Source Type: research

Exposure to Cigarette Smoke Enhances the Stemness of Alveolar Type 2 Cells.
In conclusion, we provide evidence that AT2 stem cells respond to chronic CS exposure by activating their stem cell function, thereby proliferating and differentiating faster, and becoming more resistant to apoptosis. Disturbances in expression levels of several circadian rhythm-related genes might be involved in these changes. PMID: 32338993 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - April 26, 2020 Category: Molecular Biology Authors: Tsutsumi A, Ozaki M, Chubachi S, Irie H, Sato M, Kameyama N, Sasaki M, Ishii M, Hegab AE, Betsuyaku T, Fukunaga K Tags: Am J Respir Cell Mol Biol Source Type: research

Apolipoprotein E Signals via TLR4 to Induce CXCL5 Secretion by Asthmatic Airway Epithelial Cells.
Abstract The primary function of apolipoprotein E (APOE) is to mediate the transport of cholesterol- and lipid-containing lipoprotein particles into cells by receptor-mediated endocytosis. APOE also has pro- and anti-inflammatory effects, which are both context- and concentration-dependent. For example, Apoe-/- mice have enhanced airway remodeling and hyperreactivity in experimental asthma, whereas increased APOE levels in lung epithelial lining fluid induce IL-1β secretion from human asthmatic alveolar macrophages. However, APOE-mediated airway epithelial cell inflammatory responses and signaling pathways ha...
Source: American Journal of Respiratory Cell and Molecular Biology - April 26, 2020 Category: Molecular Biology Authors: Kalchiem-Dekel O, Yao X, Barochia AV, Kaler M, Figueroa DM, Karkowsky WB, Gordon EM, Gao M, Fergusson MM, Qu X, Liu P, Li Y, Seifuddin F, Pirooznia M, Levine SJ Tags: Am J Respir Cell Mol Biol Source Type: research

MultiOMICs of WTC-Particulate Induced Persistent Airway Hyperreactivity: Role of Receptor for Advanced Glycation End Products.
Abstract Pulmonary disease after World Trade Center particulate matter(WTC-PM) exposure is associated with dyslipidemia and the receptor for advanced glycation end products (RAGE); however, the mechanisms are not well understood. We utilized a murine model and a multiOMIC assessment to understand the role of RAGE in the pulmonary long-term effects of a single high intensity exposure to WTC-PM. After 1-month(1-M), WTC-PM exposed wild-type(WT) mice had airway hyperreactivity(AHR) while RAGE-deficient(Ager-/-) were protected. PM-exposed WT mice also had histologic evidence of airspace disease while Ager-/- remained u...
Source: American Journal of Respiratory Cell and Molecular Biology - April 20, 2020 Category: Molecular Biology Authors: Haider SH, Veerappan A, Crowley G, Ostrofsky D, Mikhail M, Lam R, Wang Y, Sunseri M, Kwon S, Prezant DJ, Liu M, Schmidt AM, Nolan A Tags: Am J Respir Cell Mol Biol Source Type: research

A Call for Rational Intensive Care in the Era of COVID-19.
PMID: 32315548 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - April 20, 2020 Category: Molecular Biology Authors: Singer BD, Jain M, Budinger GRS, Wunderink RG Tags: Am J Respir Cell Mol Biol Source Type: research

S1P1 Contributes to Endotoxin-enhanced B Cell Functions Involved in Hypersensitivity Pneumonitis.
CONCLUSION: A sphingosine-1-phosphate receptor 1 ligand directly inhibits endotoxin-induced B cell activation. PMID: 32289229 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - April 13, 2020 Category: Molecular Biology Authors: Huppé CA, Blais-Lecours P, Bernatchez E, Lauzon-Joset JF, Duchaine C, Rosen H, Dion G, McNagny KM, Blanchet MR, Morissette MC, Marsolais D Tags: Am J Respir Cell Mol Biol Source Type: research

Revisiting mTOR and Epithelial-mesenchymal Transition.
PMID: 32228391 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - March 30, 2020 Category: Molecular Biology Authors: Herrerias MM, Budinger GRS Tags: Am J Respir Cell Mol Biol Source Type: research

Join or Leave the Club: Jagged1 and Notch2 Dictate the Fate of Airway Epithelial Cells.
PMID: 32228394 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - March 30, 2020 Category: Molecular Biology Authors: Kuchibhotla VN, Heijink IH Tags: Am J Respir Cell Mol Biol Source Type: research

Active mTOR in Lung Epithelium Promotes Epithelial-Mesenchymal Transition and Enhances Lung Fibrosis.
CONCLUSIONS: mTOR activation in lung epithelial cells promoted lung fibrosis and the expression of ANGPTL4, a novel downstream target of the mTOR pathway, which could be related to the etiology of fibrosis. PMID: 32208980 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - March 24, 2020 Category: Molecular Biology Authors: Saito M, Mitani A, Ishimori T, Miyashita N, Isago H, Mikami Y, Noguchi S, Tarui M, Nagase T Tags: Am J Respir Cell Mol Biol Source Type: research

Comparison of Human and Experimental Pulmonary Veno-Occlusive Disease.
In conclusion, we identified CHOP and HO-1 inhibition, and BMP9 as potential therapeutic options for PVOD. PMID: 32209028 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - March 24, 2020 Category: Molecular Biology Authors: Manaud G, Nossent EJ, Lambert M, Ghigna MR, Boët A, Vinhas MC, Ranchoux B, Dumas SJ, Courboulin A, Girerd B, Soubrier F, Bignard J, Claude O, Lecerf F, Hautefort A, Florio M, Sun B, Nadaud S, Verleden SE, Remy S, Anegon I, Bogaard HJ, Mercier O, Fadel E, Tags: Am J Respir Cell Mol Biol Source Type: research

Single Cell Flow Cytometry Profiling of Bronchoalveolar Lavage in Children.
Abstract Childhood pulmonary diseases not only cause childhood morbidity and mortality, but can also cause long term pulmonary impairment. The clinical management of many childhood pulmonary diseases is hampered by a limited understanding of the underlying pathophysiological mechanisms. Flow cytometry, which can be used to phenotype individual cell populations or isolate cells for downstream analysis, represents a crucial technology which can help to elucidate the pathophysiology of these conditions. Here, we describe a flow cytometry-based method for purification and characterisation of cell populations in bronch...
Source: American Journal of Respiratory Cell and Molecular Biology - March 23, 2020 Category: Molecular Biology Authors: Shanthikumar S, Burton M, Saffery R, Ranganathan SC, Neeland MR Tags: Am J Respir Cell Mol Biol Source Type: research

Phenotypic Diversity Caused by Differential Expression of SFTPC-Cre Transgenic Alleles.
Abstract Type II alveolar epithelial cells (AEC2s) play an essential role in the function and maintenance of the pulmonary epithelium. Several transgenic mice have been developed to study the function of these cells in vivo by using the human surfactant protein C (SFTPC) promoter to drive expression of Cre recombinase. The precise activity of each of these transgenic alleles has not been studied and previous reports suggest that their activity can depend on breeding strategies. We bred mice with a conditional allele of the essential telomere capping protein TRF2 with two different SFTPC-Cre transgenic strains and ...
Source: American Journal of Respiratory Cell and Molecular Biology - March 23, 2020 Category: Molecular Biology Authors: Jiang M, Roth MG, Chun-On P, Sullivan DI, Alder JK Tags: Am J Respir Cell Mol Biol Source Type: research

Loss of C/EBP α in Chronic Cigarette Smoke Exposure: A SAD Day for COPD.
Loss of C/EBPα in Chronic Cigarette Smoke Exposure: A SAD Day for COPD. Am J Respir Cell Mol Biol. 2020 Mar 16;: Authors: Long ME, Manicone AM PMID: 32176852 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - March 15, 2020 Category: Molecular Biology Authors: Long ME, Manicone AM Tags: Am J Respir Cell Mol Biol Source Type: research

Antisense Oligonucleotides Targeting Jagged 1 Reduce House Dust Mite-Induced Goblet Cell Metaplasia in the Adult Murine Lung.
Abstract Goblet cell metaplasia, excessive mucus production, and inadequate mucus clearance accompany and exacerbate multiple chronic respiratory disorders, such as asthma and COPD. Notch signaling plays a central role in controlling the fate of multiple cell types in the lung, including goblet cells. Here, we explored the therapeutic potential of modulating the Notch pathway in the adult murine lung using chemically-modified antisense oligonucleotides (ASOs). To this end, we designed and characterized ASOs targeting the Notch receptors Notch1, Notch2, and Notch3, and the Notch ligands Jag1 and Jag2. Pulmonary del...
Source: American Journal of Respiratory Cell and Molecular Biology - March 15, 2020 Category: Molecular Biology Authors: Carrer M, Crosby JR, Sun G, Zhao C, Damle SS, Kuntz SG, Monia BP, Hart CE, Grossman TR Tags: Am J Respir Cell Mol Biol Source Type: research

Role of Isocitrate Dehydrogenase 2 on DNA Hydroxymethylation in Human Airway Smooth Muscle Cells.
Abstract Global DNA hydroxymethylation mediated by the ten-eleven translocation (TET) enzyme was induced in allergen-induced airway hyper-responsiveness (AHR) in mouse lung tissues and specifically in isolated airway smooth muscle (ASM) cells. TET is an α-ketoglutarate (α-KG)-dependent enzyme, and the production of α-KG is catalyzed by isocitrate dehydrogenase (IDH). However, the role of IDHs in the regulation of DNA hydroxymethylation in ASM cells is unknown. In comparison with non-asthmatic cells, asthmatic ASM cells exhibited a higher TET activity and IDH2 (not IDH-1 and -3) gene expression le...
Source: American Journal of Respiratory Cell and Molecular Biology - March 8, 2020 Category: Molecular Biology Authors: Yeung BH, Huang J, An SS, Solway J, Mitzner W, Tang WY Tags: Am J Respir Cell Mol Biol Source Type: research

The Roles of ORMDL3 in Rhinovirus Infections.
PMID: 32109135 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - February 27, 2020 Category: Molecular Biology Authors: Ito K, Zhang Y Tags: Am J Respir Cell Mol Biol Source Type: research

Pneumocystis Pneumonia: Checkpoint Inhibition to the Rescue?
PMID: 32109143 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - February 27, 2020 Category: Molecular Biology Authors: Better J, Matt U Tags: Am J Respir Cell Mol Biol Source Type: research

Extracellular Vesicles: A New Frontier for Research in Acute Respiratory Distress Syndrome.
Abstract Recent research on extracellular vesicles (EVs) has provided new insights into pathogenesis and potential therapeutic options for acute respiratory distress syndrome (ARDS). EVs are membrane-bound anuclear structures which carry important inter-cellular communication mechanisms, allowing targeted transfer of diverse biologic cargo including protein, mRNA and microRNA among several different cell types. In this review, we discuss the important role EVs play in both inducing and attenuating inflammatory lung injury in ARDS as well as in sepsis, the most important clinical cause of ARDS. We discuss the trans...
Source: American Journal of Respiratory Cell and Molecular Biology - February 27, 2020 Category: Molecular Biology Authors: Mahida RY, Matsumoto S, Matthay MA Tags: Am J Respir Cell Mol Biol Source Type: research

Mural Cell SDF1 Signaling is Associated with the Pathogenesis of Pulmonary Arterial Hypertension.
CONCLUSION: SDF1 is upregulated in NG2+ mural cells and is associated with PA muscularization. Targeting SDF1 could help prevent and/or reverse muscularization in PAH. PMID: 32084325 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - February 20, 2020 Category: Molecular Biology Authors: Yuan K, Liu Y, Zhang Y, Nathan A, Tian W, Yu J, Sweatt AJ, Condon D, Chakraborty A, Agarwal S, Auer N, Zhang S, Wu JC, Zamanian RT, Nicolls MR, de Jesus Perez VA Tags: Am J Respir Cell Mol Biol Source Type: research

Regulated Necrosis in Pulmonary Disease: A Focus on Necroptosis and Ferroptosis.
Abstract To date, increasing evidence suggests the possible involvement of various types of cell death in lung diseases. The recognized regulated cell death (RCD) includes necrotic cell death that is immunogenic, releasing damage-associated molecular patterns (DAMPs) and driving tissue inflammation. Necroptosis is a well-understood form of regulated necrosis that is executed by receptor interacting protein kinase 3 (RIPK3) and the pseudo kinase mixed lineage kinase domain-like protein (MLKL). Ferroptosis is a newly described caspase-independent form of regulated necrosis that is characterized by the increase of de...
Source: American Journal of Respiratory Cell and Molecular Biology - February 3, 2020 Category: Molecular Biology Authors: Minagawa S, Yoshida M, Araya J, Hara H, Imai H, Kuwano K Tags: Am J Respir Cell Mol Biol Source Type: research

Recommended Reading from the University College Dublin and St. Vincent's University Hospital Pulmonary Research Fellows.
PMID: 32017596 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - February 3, 2020 Category: Molecular Biology Authors: O'Reilly A, Sahadevan A, Shah W, Keane MP, McCarthy C Tags: Am J Respir Cell Mol Biol Source Type: research

Is Phosphatidylinositol 3- kinase (PI3K) a Villain in Cystic Fibrosis?
PMID: 32011906 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - February 2, 2020 Category: Molecular Biology Authors: Natarajan V Tags: Am J Respir Cell Mol Biol Source Type: research

Cholesterol - A Novel Regulator of Vasoreactivity in Pulmonary Arteries.
PMID: 32011912 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - February 2, 2020 Category: Molecular Biology Authors: Grimmer B, Kuebler WM Tags: Am J Respir Cell Mol Biol Source Type: research