Epithelial Cell Mitochondrial Dysfunction and PINK1 Are Induced by Transforming Growth Factor- Beta1 in Pulmonary Fibrosis

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Epithelial Cell Mitochondrial Dysfunction and PINK1 Are Induced by Transforming Growth Factor- Beta1 in Pulmonary Fibrosis

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Title: Epithelial Cell Mitochondrial Dysfunction and PINK1 Are Induced by Transforming Growth Factor- Beta1 in Pulmonary Fibrosis
Author: Patel, Avignat S.; Song, Jin Woo; Chu, Sarah G.; Mizumura, Kenji; Osorio, Juan C.; Shi, Ying; El-Chemaly, Souheil; Lee, Chun Geun; Rosas, Ivan O.; Elias, Jack A.; Choi, Augustine M. K.; Morse, Danielle

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Citation: Patel, A. S., J. W. Song, S. G. Chu, K. Mizumura, J. C. Osorio, Y. Shi, S. El-Chemaly, et al. 2015. “Epithelial Cell Mitochondrial Dysfunction and PINK1 Are Induced by Transforming Growth Factor- Beta1 in Pulmonary Fibrosis.” PLoS ONE 10 (3): e0121246. doi:10.1371/journal.pone.0121246. http://dx.doi.org/10.1371/journal.pone.0121246.
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Abstract: Background: Epithelial cell death is a major contributor to fibrogenesis in the lung. In this study, we sought to determine the function of mitochondria and their clearance (mitophagy) in alveolar epithelial cell death and fibrosis. Methods: We studied markers of mitochondrial injury and the mitophagy marker, PTEN-induced putative kinase 1 (PINK1), in IPF lung tissues by Western blotting, transmission electron microscopy (TEM), and immunofluorescence. In vitro experiments were carried out in lung epithelial cells stimulated with transforming growth factor-β1 (TGF-β1). Changes in cell function were measured by Western blotting, flow cytometry and immunofluorescence. In vivo experiments were performed using the murine bleomycin model of lung fibrosis. Results: Evaluation of IPF lung tissue demonstrated increased PINK1 expression by Western blotting and immunofluorescence and increased numbers of damaged mitochondria by TEM. In lung epithelial cells, TGF-β1 induced mitochondrial depolarization, mitochondrial ROS, and PINK1 expression; all were abrogated by mitochondrial ROS scavenging. Finally, Pink1-/- mice were more susceptible than control mice to bleomycin induced lung fibrosis. Conclusion: TGF-β1 induces lung epithelial cell mitochondrial ROS and depolarization and stabilizes the key mitophagy initiating protein, PINK1. PINK1 ameliorates epithelial cell death and may be necessary to limit fibrogenesis.
Published Version: doi:10.1371/journal.pone.0121246
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364993/pdf/
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Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:14351320
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