| First Author | Lee MR | Year | 2014 |
| Journal | Cell Death Dis | Volume | 5 |
| Pages | e1113 | PubMed ID | 24625972 |
| Mgi Jnum | J:315528 | Mgi Id | MGI:6829161 |
| Doi | 10.1038/cddis.2014.86 | Citation | Lee MR, et al. (2014) BAX inhibitor-1-associated V-ATPase glycosylation enhances collagen degradation in pulmonary fibrosis. Cell Death Dis 5:e1113 |
| abstractText | Endoplasmic reticulum (ER) stress is considered one of the pathological mechanisms of idiopathic pulmonary fibrosis (IPF). Therefore, we examined whether an ER stress regulator, Bax inhibitor-1 (BI-1), regulates collagen accumulation, which is both a marker of fibrosis and a pathological mechanism of fibrosis. The presence of BI-1 inhibited the transforming growth factor-beta1-induced epithelial-mesenchymal transition of epithelial pulmonary cells and bleomycin-induced pulmonary fibrosis in a mouse model by enhancing collagen degradation, most likely by enhanced activation of the lysosomal V-ATPase through glycosylation. We also found a correlation between post-translational glycosylation of the V-ATPase and its associated chaperone, calnexin, in BI-1-overexpressing cells. BI-1-induced degradation of collagen through lysosomal V-ATPase glycosylation and the involvement of calnexin were confirmed in a bleomycin-induced fibrosis mouse model. These results highlight the regulatory role of BI-1 in IPF and reveal for the first time the role of lysosomal V-ATPase glycosylation in IPF. |
