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Source: AJP: Lung Cellular and Molecular Physiology
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Total 59 results found since Jan 2013.
CYP2E1 regulates the development of radiation-induced pulmonary fibrosis via ER stress- and ROS-dependent mechanisms
This study was conducted to identify the molecular mechanism responsible for RIPF. We revealed that the transcriptional level of cytochrome P450 2E1 (CYP2E1) was elevated by examining expression profile analysis of RIPF mouse models. We also confirmed that CYP2E1 regulated levels of endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) in alveolar epithelial type II (AE2) cells and lung fibroblasts. Inhibition of CYP2E1 via its siRNA or inhibitor significantly attenuated epithelial-to-mesenchymal transition and apoptosis of AE2 cells, as well as myofibroblast formation induced by radiation. Finally, the effec...
Source: AJP: Lung Cellular and Molecular Physiology - November 6, 2017 Category: Respiratory Medicine Authors: Son, B., Kwon, T., Lee, S., Han, I., Kim, W., Youn, H., Youn, B. Tags: RESEARCH ARTICLE Source Type: research
Distinct PKA regulatory subunits mediate PGE2 inhibition of TGF{beta}-1-stimulated collagen I translation and myofibroblast differentiation
Prostaglandin E2 (PGE2), via cAMP signaling, inhibits a variety of fibroblast functions relevant to fibrogenesis. Among these are their translation of collagen I protein and their differentiation to myofibroblasts. PKA is central to these actions, with cAMP binding to regulatory (R) subunits leading to the release of catalytic subunits. Here we examined the role of specific PKAR subunit isoforms in these inhibitory actions in transforming growth factor β-1 (TGFβ-1)-stimulated human lung fibroblasts (HLFs). HLFs expressed all four R subunit isoforms. siRNA-mediated knockdown of subunits PKARIα and PKARII&alp...
Source: AJP: Lung Cellular and Molecular Physiology - October 1, 2017 Category: Respiratory Medicine Authors: Wettlaufer, S. H., Penke, L. R., Okunishi, K., Peters-Golden, M. Tags: RESEARCH ARTICLE Source Type: research
Estrogen and cigarette sidestream smoke particulate matter exhibit ER{alpha}-dependent tumor-promoting effects in lung adenocarcinoma cells
This study demonstrates that estrogen has ERα-dependent tumor-promoting activity. CSSP acts like estrogen and shows a potential to enhance estrogen-induced ERα action.
Source: AJP: Lung Cellular and Molecular Physiology - September 1, 2017 Category: Respiratory Medicine Authors: Kuo, L.-C., Cheng, L.-C., Lee, C.-H., Lin, C.-J., Chen, P.-Y., Li, L.-A. Tags: RESEARCH ARTICLE Source Type: research
Peroxisome proliferator-activated receptor-{gamma} enhances human pulmonary artery smooth muscle cell apoptosis through microRNA-21 and programmed cell death 4
Pulmonary hypertension (PH) is a progressive disorder whose cellular pathogenesis involves enhanced smooth muscle cell (SMC) proliferation and resistance to apoptosis signals. Existing evidence demonstrates that the tumor suppressor programmed cell death 4 (PDCD4) affects patterns of cell growth and repair responses in the systemic vasculature following experimental injury. In the current study, the regulation PDCD4 and its functional effects on growth and apoptosis susceptibility in pulmonary artery smooth muscle cells were explored. We previously demonstrated that pharmacological activation of the nuclear transcription f...
Source: AJP: Lung Cellular and Molecular Physiology - August 1, 2017 Category: Respiratory Medicine Authors: Green, D. E., Murphy, T. C., Kang, B.-Y., Bedi, B., Yuan, Z., Sadikot, R. T., Hart, C. M. Tags: RESEARCH ARTICLE Source Type: research
Autophagy plays a role in FSTL1-induced epithelial mesenchymal transition and airway remodeling in asthma
In this study, we hypothesized that Follistatin-like 1 (FSTL1) promotes EMT and airway remodeling by intensifying autophagy. With the use of transmission electron microscopy (TEM), double-membrane autophagosomes were detected in the airways of patients and mice. More autophagosomes were in patients with asthma and OVA-challenged mice compared with healthy controls. The expression of FSTL1 and beclin-1 was upregulated in the airways of patients with asthma and OVA-challenged mice, accompanied by airway EMT and remodeling. In OVA-challenged Fstl1+/– mice, the degree of airway remodeling and autophagy was decreased comp...
Source: AJP: Lung Cellular and Molecular Physiology - July 1, 2017 Category: Respiratory Medicine Authors: Liu, T., Liu, Y., Miller, M., Cao, L., Zhao, J., Wu, J., Wang, J., Liu, L., Li, S., Zou, M., Xu, J., Broide, D. H., Dong, L. Tags: RESEARCH ARTICLE Source Type: research
Focal adhesion kinase signaling determines the fate of lung epithelial cells in response to TGF-{beta}
In this report, we explore the role of focal adhesion kinase (FAK) signaling in determining the fate of lung epithelial cells in response to transforming growth factor-β1 (TGF-β1). Rat type II alveolar epithelial cells (RLE-6TN) were treated with or without TGF-β1, and the expressions of mesenchymal markers, phenotype, and function were analyzed. Pharmacological protein kinase inhibitors were utilized to screen for SMAD-dependent and -independent pathways. SMAD and FAK signaling was analyzed using siRNA knockdown, inhibitors, and expression of a mutant construct of FAK. Apoptosis was measured using cleaved c...
Source: AJP: Lung Cellular and Molecular Physiology - June 5, 2017 Category: Respiratory Medicine Authors: Ding, Q., Subramanian, I., Luckhardt, T. R., Che, P., Waghray, M., Zhao, X.-K., Bone, N., Kurundkar, A. R., Hecker, L., Hu, M., Zhou, Y., Horowitz, J. C., Vittal, R., Thannickal, V. J. Tags: RESEARCH ARTICLE Source Type: research
Sirtuin 7 is decreased in pulmonary fibrosis and regulates the fibrotic phenotype of lung fibroblasts
In conclusion, the decline in SIRT7 in lung fibroblasts has a profibrotic effect, which is mediated by changes in Smad3 levels.
Source: AJP: Lung Cellular and Molecular Physiology - June 5, 2017 Category: Respiratory Medicine Authors: Wyman, A. E., Noor, Z., Fishelevich, R., Lockatell, V., Shah, N. G., Todd, N. W., Atamas, S. P. 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
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
Ca2+/calmodulin-dependent protein kinase II{beta} and II{delta} mediate TGF{beta}-induced transduction of fibronectin and collagen in human pulmonary fibroblasts
In this study, we examined the interactions between calcium signaling, activation of CamK and other kinases, and extracellular matrix (ECM) gene expression. Human pulmonary fibroblasts were cultured and stimulated with artificially generated Ca2+ pulses in the absence of TGFβ, or with TGFβ (1 nM) or vehicle in the presence of various blockers of Ca2+ signaling. PCR and Western blotting were used to measure gene expression and protein levels, respectively. We found that Ca2+ pulses in the absence of TGFβ increased ECM gene expression in a pulse frequency-dependent manner, and that blocking Ca2+ signaling and ...
Source: AJP: Lung Cellular and Molecular Physiology - April 1, 2017 Category: Respiratory Medicine Authors: Mukherjee, S., Sheng, W., Sun, R., Janssen, L. J. Tags: RESEARCH ARTICLE Source Type: research
Hyperoxia-induced p47phox activation and ROS generation is mediated through S1P transporter Spns2, and S1P/S1P1 signaling axis in lung endothelium
Hyperoxia-induced lung injury adversely affects ICU patients and neonates on ventilator assisted breathing. The underlying culprit appears to be reactive oxygen species (ROS)-induced lung damage. The major contributor of hyperoxia-induced ROS is activation of the multiprotein enzyme complex NADPH oxidase. Sphingosine-1-phosphate (S1P) signaling is known to be involved in hyperoxia-mediated ROS generation; however, the mechanism(s) of S1P-induced NADPH oxidase activation is unclear. Here, we investigated various steps in the S1P signaling pathway mediating ROS production in response to hyperoxia in lung endothelium. Of the ...
Source: AJP: Lung Cellular and Molecular Physiology - July 31, 2016 Category: Respiratory Medicine Authors: Harijith, A., Pendyala, S., Ebenezer, D. L., Ha, A. W., Fu, P., Wang, Y.-T., Ma, K., Toth, P. T., Berdyshev, E. V., Kanteti, P., Natarajan, V. Tags: CALL FOR PAPERS Source Type: research
Histone deacetylation contributes to low extracellular superoxide dismutase expression in human idiopathic pulmonary arterial hypertension
Epigenetic mechanisms, including DNA methylation and histone acetylation, regulate gene expression in idiopathic pulmonary arterial hypertension (IPAH). These mechanisms can modulate expression of extracellular superoxide dismutase (SOD3 or EC-SOD), a key vascular antioxidant enzyme, and loss of vascular SOD3 worsens outcomes in animal models of pulmonary arterial hypertension. We hypothesized that SOD3 gene expression is decreased in patients with IPAH due to aberrant DNA methylation and/or histone deacetylation. We used lung tissue and pulmonary artery smooth muscle cells (PASMC) from subjects with IPAH at transplantatio...
Source: AJP: Lung Cellular and Molecular Physiology - June 30, 2016 Category: Respiratory Medicine Authors: Nozik-Grayck, E., Woods, C., Stearman, R. S., Venkataraman, S., Ferguson, B. S., Swain, K., Bowler, R. P., Geraci, M. W., Ihida-Stansbury, K., Stenmark, K. R., McKinsey, T. A., Domann, F. E. Tags: ARTICLES Source Type: research
Chronic high-magnitude cyclic stretch stimulates EC inflammatory response via VEGF receptor 2-dependent mechanism
This study demonstrates for the first time a VEGFR2-dependent mechanism of EC inflammatory activation induced by pathological CS. We conclude that, despite the recognized role of VEGF as a prosurvival and angiogenic factor, excessive activation of VEGFR2 signaling by high-tidal-volume lung mechanical ventilation may contribute to ventilator-induced (biotrauma) lung inflammation and barrier dysfunction by augmenting cell response to VILI-associated inflammatory mediators.
Source: AJP: Lung Cellular and Molecular Physiology - May 31, 2016 Category: Respiratory Medicine Authors: Gawlak, G., Son, S., Tian, Y., O'Donnell, J. J., Birukov, K. G., Birukova, A. A. Tags: CALL FOR PAPERS Source Type: research
Pathogenic role of calcium-sensing receptors in the development and progression of pulmonary hypertension
An increase in cytosolic free Ca2+ concentration ([Ca2+]cyt) in pulmonary arterial smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction and a critical stimulation for PASMC proliferation and migration. Previously, we demonstrated that expression and function of calcium sensing receptors (CaSR) in PASMC from patients with idiopathic pulmonary arterial hypertension (IPAH) and animals with experimental pulmonary hypertension (PH) were greater than in PASMC from normal subjects and control animals. However, the mechanisms by which CaSR triggers Ca2+ influx in PASMC and the implication of CaSR in the de...
Source: AJP: Lung Cellular and Molecular Physiology - April 30, 2016 Category: Respiratory Medicine Authors: Tang, H., Yamamura, A., Yamamura, H., Song, S., Fraidenburg, D. R., Chen, J., Gu, Y., Pohl, N. M., Zhou, T., Jimenez-Perez, L., Ayon, R. J., Desai, A. A., Goltzman, D., Rischard, F., Khalpey, Z., Black, S. M., Garcia, J. G. N., Makino, A., Yuan, J. X. J. Tags: ARTICLES Source Type: research
The Src family tyrosine kinases src and yes have differential effects on inflammation-induced apoptosis in human pulmonary microvascular endothelial cells
Endothelial cells are essential for normal lung function: they sense and respond to circulating factors and hemodynamic alterations. In inflammatory lung diseases such as acute respiratory distress syndrome, endothelial cell apoptosis is an inciting event in pathogenesis and a prominent pathological feature. Endothelial cell apoptosis is mediated by circulating inflammatory factors, which bind to receptors on the cell surface, activating signal transduction pathways, leading to caspase-3-mediated apoptosis. We hypothesized that yes and src have differential effects on caspase-3 activation in human pulmonary microvascular e...
Source: AJP: Lung Cellular and Molecular Physiology - April 30, 2016 Category: Respiratory Medicine Authors: Nelin, L. D., White, H. A., Jin, Y., Trittmann, J. K., Chen, B., Liu, Y. Tags: ARTICLES Source Type: research
