Epithelial Cell Mitochondrial Dysfunction and PINK1 Are Induced by Transforming Growth Factor- Beta1 in Pulmonary Fibrosis
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Author
Patel, Avignat S.
Song, Jin Woo
Mizumura, Kenji
Osorio, Juan C.
Lee, Chun Geun
Elias, Jack A.
Choi, Augustine M. K.
Morse, Danielle
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1371/journal.pone.0121246Metadata
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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.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364993/pdf/Terms of Use
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