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Source: AJP: Lung Cellular and Molecular Physiology
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Total 59 results found since Jan 2013.
Silencing of MUC8 by siRNA increases P2Y2-induced airway inflammation
Mucin hypersecretion and overproduction are frequent manifestations of respiratory disease. Determining the physiological function of airway mucin is presently considered more important than identifying the relevant signaling pathways. The lack of a full-length human mucin 8 (MUC8) cDNA sequence has hindered the generation of a Muc8 knockout mouse line. Thus, the precise physiological functions of MUC8 are unclear. Herein, we investigated the function of MUC8 using a small-interfering RNA (siRNA)-mediated genetic silencing approach in human airway epithelial cells. Herein, intracellular IL-1α production was stimulate...
Source: AJP: Lung Cellular and Molecular Physiology - March 15, 2015 Category: Respiratory Medicine Authors: Cha, H.-J., Jung, M.-S., Ahn, D. W., Choi, J.-K., Ock, M. S., Kim, K. S., Yoon, J.-H., Song, E. J., Song, K. S. Tags: CALL FOR PAPERS Source Type: research
The p66Shc adapter protein regulates the morphogenesis and epithelial maturation of fetal mouse lungs
Many signaling pathways are mediated by Shc adapter proteins that, in turn, are expressed as three isoforms with distinct functions. The p66Shc isoform antagonizes proliferation, regulates oxidative stress, and mediates apoptosis. It is highly expressed in the canalicular but not the later stages of mouse lung development, and its expression persists in bronchopulmonary dysplasia, a chronic disease associated with premature birth. These observations suggest that p66Shc has a developmental function. However, constitutive p66Shc deletion yields no morphological phenotype, and the structure of the Shc gene precludes its induc...
Source: AJP: Lung Cellular and Molecular Physiology - February 15, 2014 Category: Respiratory Medicine Authors: Lee, M. K., Smith, S. M., Banerjee, M. M., Li, C., Minoo, P., Volpe, M. V., Nielsen, H. C. Tags: ARTICLES Source Type: research
Endothelin-1 decreases endothelial PPAR{gamma} signaling and impairs angiogenesis after chronic intrauterine pulmonary hypertension
Increased endothelin-1 (ET-1) disrupts angiogenesis in persistent pulmonary hypertension of the newborn (PPHN), but pathogenic mechanisms are unclear. Peroxisome proliferator activated receptor (PPAR) is decreased in adult pulmonary hypertension, but whether ET-1-PPAR interactions impair endothelial cell function and angiogenesis in PPHN remains unknown. We hypothesized that increased PPHN pulmonary artery endothelial cell (PAEC) ET-1 production decreases PPAR signaling and impairs tube formation in vitro. Proximal PAECs were harvested from fetal sheep after partial ligation of the ductus arteriosus in utero (PPHN) and con...
Source: AJP: Lung Cellular and Molecular Physiology - February 15, 2014 Category: Respiratory Medicine Authors: Wolf, D., Tseng, N., Seedorf, G., Roe, G., Abman, S. H., Gien, J. Tags: ARTICLES Source Type: research
Nox2/ROS-dependent human antigen R translocation contributes to TNF-{alpha}-induced SOCS-3 expression in human tracheal smooth muscle cells
Elevated levels of TNF-α have been detected in the airway fluids, which may induce upregulation of inflammatory proteins. Suppressors of cytokine signaling (SOCS)-3 proteins can be induced by various cytokines and negatively regulated inflammatory responses. Although TNF-α has been shown to induce SOCS-3 expression, the mechanisms underlying TNF-α-induced SOCS-3 expression in human tracheal smooth muscle cells (HTSMCs) remain unclear. Here, we showed that TNF-α induced SOCS-3 expression, which was inhibited by pretreatment with the inhibitor of transcription level (actinomycin D), translation level ...
Source: AJP: Lung Cellular and Molecular Physiology - March 15, 2014 Category: Respiratory Medicine Authors: Hsu, C.-K., Lee, I.-T., Lin, C.-C., Hsiao, L.-D., Yang, C.-M. Tags: ARTICLES Source Type: research
c-Abl mediated tyrosine phosphorylation of paxillin regulates LPS-induced endothelial dysfunction and lung injury
Paxillin is phosphorylated at multiple residues; however, the role of tyrosine phosphorylation of paxillin in endothelial barrier dysfunction and acute lung injury (ALI) remains unclear. We used siRNA and site-specific nonphosphorylable mutants of paxillin to abrogate the function of paxillin to determine its role in lung endothelial permeability and ALI. In vitro, lipopolysaccharide (LPS) challenge of human lung microvascular endothelial cells (HLMVECs) resulted in enhanced tyrosine phosphorylation of paxillin at Y31 and Y118 with no significant change in Y181 and significant barrier dysfunction. Knockdown of paxillin wit...
Source: AJP: Lung Cellular and Molecular Physiology - May 15, 2015 Category: Respiratory Medicine Authors: Fu, P., Usatyuk, P. V., Lele, A., Harijith, A., Gregorio, C. C., Garcia, J. G. N., Salgia, R., Natarajan, V. Tags: CALL FOR PAPERS Source Type: research
Neutral sphingomyelinase 2 is required for cytokine-induced skeletal muscle calpain activation
Calpain contributes to infection-induced diaphragm dysfunction but the upstream mechanism(s) responsible for calpain activation are poorly understood. It is known, however, that cytokines activate neutral sphingomyelinase (nSMase) and nSMase has downstream effects with the potential to increase calpain activity. We tested the hypothesis that infection-induced skeletal muscle calpain activation is a consequence of nSMase activation. We administered cytomix (20 ng/ml TNF-α, 50 U/ml IL-1β, 100 U/ml IFN-, 10 μg/ml LPS) to C2C12 muscle cells to simulate the effects of infection in vitro and studied mice undergoing...
Source: AJP: Lung Cellular and Molecular Physiology - September 15, 2015 Category: Respiratory Medicine Authors: Supinski, G. S., Alimov, A. P., Wang, L., Song, X.-H., Callahan, L. A. Tags: ARTICLES Source Type: research
Protocadherin-1 binds to SMAD3 and suppresses TGF-{beta}1-induced gene transcription
In conclusion, we demonstrate that PCDH1 binds to SMAD3 and regulates its activation by TGF-β signaling in bronchial epithelial cells. We propose that PCDH1 and SMAD3 act in a single pathway in asthma susceptibility that affects sensitivity of the airway epithelium to TGF-β.
Source: AJP: Lung Cellular and Molecular Physiology - October 1, 2015 Category: Respiratory Medicine Authors: Faura Tellez, G., Vandepoele, K., Brouwer, U., Koning, H., Elderman, R. M., Hackett, T.-L., Willemse, B. W. M., Holloway, J., Van Roy, F., Koppelman, G. H., Nawijn, M. C. Tags: ARTICLES Source Type: research
Hypoxia induces arginase II expression and increases viable human pulmonary artery smooth muscle cell numbers via AMPK{alpha}1 signaling
Pulmonary artery smooth muscle cell (PASMC) proliferation is one of the hallmark features of hypoxia-induced pulmonary hypertension. With only supportive treatment options available for this life-threatening disease, treating and preventing the proliferation of PASMCs is a viable therapeutic option. A key promoter of hypoxia-induced increases in the number of viable human PASMCs is arginase II, with attenuation of viable cell numbers following pharmacologic inhibition or siRNA knockdown of the enzyme. Additionally, increased levels of arginase have been demonstrated in the pulmonary vasculature of patients with pulmonary h...
Source: AJP: Lung Cellular and Molecular Physiology - April 5, 2017 Category: Respiratory Medicine Authors: Xue, J., Nelin, L. D., Chen, B. Tags: RESEARCH ARTICLE Source Type: research
Hypoxic proliferation requires EGFR-mediated ERK activation in human pulmonary microvascular endothelial cells
We have previously shown that hypoxic proliferation of human pulmonary microvascular endothelial cells (hPMVECs) depends on epidermal growth factor receptor (EGFR) activation. To determine downstream signaling leading to proliferation, we tested the hypothesis that hypoxia-induced proliferation in hPMVECs would require EGFR-mediated activation of extracellular signal-regulated kinase (ERK) leading to arginase II induction. To test this hypothesis, hPMVECs were incubated in either normoxia (21% O2, 5% CO2) or hypoxia (1% O2, 5% CO2) and Western blotting was performed for EGFR, arginase II, phosphorylated-ERK (pERK), and tot...
Source: AJP: Lung Cellular and Molecular Physiology - May 1, 2017 Category: Respiratory Medicine Authors: White, H. A., Jin, Y., Chicoine, L. G., Chen, B., Liu, Y., Nelin, L. D. Tags: RESEARCH ARTICLE Source Type: research
IL-13 receptor {alpha}2-arginase 2 pathway mediates IL-13-induced pulmonary hypertension
This study's goal was to investigate the role and mechanism of IL-13 in the pathogenesis of PH. Lung-specific IL-13-overexpressing transgenic (Tg) mice were examined for hemodynamic changes and pulmonary vascular remodeling. IL-13 Tg mice spontaneously developed PH phenotype by the age of 2 mo with increased expression and activity of arginase 2 (Arg2). The role of Arg2 in the development of IL-13-stimulated PH was further investigated using Arg2 and IL-13 receptor α2 (Rα2) null mutant mice and the small-interfering RNA (siRNA)-silencing approach in vivo and in vitro, respectively. IL-13-stimulated medial thick...
Source: AJP: Lung Cellular and Molecular Physiology - January 15, 2013 Category: Respiratory Medicine Authors: Cho, W.-K., Lee, C.-M., Kang, M.-J., Huang, Y., Giordano, F. J., Lee, P. J., Trow, T. K., Homer, R. J., Sessa, W. C., Elias, J. A., Lee, C. G. Tags: ARTICLES Source Type: research
Nicotine-induced epithelial-mesenchymal transition via Wnt/{beta}-catenin signaling in human airway epithelial cells
Epithelial-mesenchymal transition (EMT) has been proposed to be a mechanism in airway remodeling, which is a characteristic of chronic obstructive pulmonary disease (COPD). Studies have shown that cigarette smoke and nicotine are factors that induce Wnt/β-catenin activation, which is a pathway that has also been implicated in EMT. The main aim of this study was to test whether human bronchial epithelial cells are able to undergo EMT in vitro following nicotine stimulation via the Wnt3a/β-catenin signaling pathway. We show that nicotine activates the Wnt3a signal pathway, which leads to the translocation of β...
Source: AJP: Lung Cellular and Molecular Physiology - February 15, 2013 Category: Respiratory Medicine Authors: Zou, W., Zou, Y., Zhao, Z., Li, B., Ran, P. Tags: CALL FOR PAPERS Source Type: research
MARCKS and HSP70 interactions regulate mucin secretion by human airway epithelial cells in vitro
Myristoylated alanine-rich C kinase substrate (MARCKS) protein has been recognized as a key regulatory molecule controlling mucin secretion by airway epithelial cells in vitro and in vivo. We recently showed that two intracellular chaperones, heat shock protein 70 (HSP70) and cysteine string protein (CSP), associate with MARCKS in the secretory mechanism. To elucidate more fully MARCKS-HSP70 interactions in this process, studies were performed in well-differentiated normal human bronchial epithelial (NHBE) cells maintained in air-liquid interface culture utilizing specific pharmacological inhibition of HSP70 with pyrimidin...
Source: AJP: Lung Cellular and Molecular Physiology - April 15, 2013 Category: Respiratory Medicine Authors: Fang, S., Crews, A. L., Chen, W., Park, J., Yin, Q., Ren, X.-R., Adler, K. B. Tags: ARTICLES Source Type: research
Efficient delivery of RNA interference oligonucleotides to polarized airway epithelia in vitro
Polarized and pseudostratified primary airway epithelia present barriers that significantly reduce their transfection efficiency and the efficacy of RNA interference oligonucleotides. This creates an impediment in studies of the airway epithelium, diminishing the utility of loss-of-function as a research tool. Here we outline methods to introduce RNAi oligonucleotides into primary human and porcine airway epithelia grown at an air-liquid interface and difficult-to-transfect transformed epithelial cell lines grown on plastic. At the time of plating, we reverse transfect small-interfering RNA (siRNA), Dicer-substrate siRNA, ...
Source: AJP: Lung Cellular and Molecular Physiology - July 1, 2013 Category: Respiratory Medicine Authors: Ramachandran, S., Krishnamurthy, S., Jacobi, A. M., Wohlford-Lenane, C., Behlke, M. A., Davidson, B. L., McCray, P. B. Tags: INNOVATIVE METHODOLOGY Source Type: research
Id proteins are critical downstream effectors of BMP signaling in human pulmonary arterial smooth muscle cells
In conclusion, Id proteins, and particularly Id1 and Id3, are critical downstream effectors of BMP signaling in PASMCs. Loss of BMPR-II function reduces the induction of Id genes in PASMCs, Id1, and Id3 regulate the proliferation of PASMCs via cell cycle inhibition, an effect that may be exacerbated by inflammatory stimuli.
Source: AJP: Lung Cellular and Molecular Physiology - August 15, 2013 Category: Respiratory Medicine Authors: Yang, J., Li, X., Li, Y., Southwood, M., Ye, L., Long, L., Al-Lamki, R. S., Morrell, N. W. Tags: ARTICLES Source Type: research
Transdifferentiation of alveolar epithelial type II to type I cells is controlled by opposing TGF-{beta} and BMP signaling
Alveolar epithelial type II (ATII) cells are essential for maintaining normal lung homeostasis because they produce surfactant, express innate immune proteins, and can function as progenitors for alveolar epithelial type I (ATI) cells. Although autocrine production of transforming growth factor (TGF)-β1 has been shown to promote the transdifferentiation of primary rat ATII to ATI cells in vitro, mechanisms controlling this process still remain poorly defined. Here, evidence is provided that Tgf-β1, -2, -3 mRNA and phosphorylated SMAD2 and SMAD3 significantly increase as primary cultures of mouse ATII cells transd...
Source: AJP: Lung Cellular and Molecular Physiology - September 15, 2013 Category: Respiratory Medicine Authors: Zhao, L., Yee, M., O'Reilly, M. A. Tags: ARTICLES Source Type: research
