Overexpression of ISCU can extenuate mitochondrial damage, reduce EMT and bleomycin-induced pulmonary fibrosis

Abstract

Background: The EMT process plays a crucial role in the pathogenesis of IPF. Current research has found that excessive oxidative stress caused by mitochondrial damage may be an important reason for the excessive progress of EMT in pulmonary fibrosis. In our previous studies, we found that the expression of iscu was significantly down-regulated in the bleomycin-induced rhesus pulmonary fibrosis model. Aim: The goal of this study is to reveal whether it is possible to affect mitochondrial damage, EMT and pulmonary fibrosis in vivo and in vitro by regulating the expression of iscu. Methods: We used TGF-β to stimulate EMT in rat alveolar type II cells (AT II), and BLM was used to induce rat pulmonary fibrosis. ISCU adenovirus overexpression vector was used to infect ATII cells and rats for iscu over expression. We examined related indicators of EMT, pulmonary fibrosis, and mitochondrial damage in vivo and in vitro. Results: After the stimulation of TGF-β or BLM, the content of ISCU in ATII cells and rat lung decreased significantly, and caused significant mitochondrial damage. In ATII cells and rats infected with the iscu adenovirus overexpression vector, the degree of mitochondrial damage was significantly extenuated, and the levels of pulmonary fibrosis and EMT were also significantly reduced. Conclusion: We believe that iscu can regulate the progression of EMT, the development of pulmonary fibrosis and extenuate mitochondrial damage. We speculate that iscu can reduce EMT and pulmonary fibrosis by regulating mitochondrial damage. In future work, we will try to reveal the relationship between iscu, iron metabolism and mitochondrial damage.