PINK1 Are Induced by Transforming Growth Factor- Beta1 in Pulmonary Fibrosis

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 epithe-lial cell death and fibrosis. Methods We studied markers of mitochondrial injury and the mitophagy marker, PTEN-induced puta-tive kinase 1 (PINK1), in IPF lung tissues by Western blotting, transmission electron micros-copy (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 blot-ting 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