| First Author | Lee JU | Year | 2022 |
| Journal | Exp Mol Med | Volume | 54 |
| Issue | 5 | Pages | 662-672 |
| PubMed ID | 35624153 | Mgi Jnum | J:326261 |
| Mgi Id | MGI:7293400 | Doi | 10.1038/s12276-022-00776-2 |
| Citation | Lee JU, et al. (2022) Overexpression of V-ATPase B2 attenuates lung injury/fibrosis by stabilizing lysosomal membrane permeabilization and increasing collagen degradation. Exp Mol Med 54(5):662-672 |
| abstractText | Excessive oxidative stress causes lysosomal membrane permeabilization (LMP), which leads to cell death. Vacuolar ATPase (V-ATPase) is the enzyme responsible for pumping H(+) into the cytosol and thus maintaining intracellular pH. Previously, we reported that V-ATPase B2 subunit expression is upregulated in the TiO2-exposed lung epithelium. We investigated the role of the lysosomal V-ATPase B2 subunit in oxidative stress-induced alveolar epithelial cell death and in an experimental lung injury/fibrosis model. Overexpression of V-ATPase B2 increased lysosomal pH and lysosomal activities in the cells. In the presence of H2O2, overexpression of V-ATPase B2 increased survival, and silencing of V-ATPase B2 dramatically increased cell death. Overexpression of V-ATPase B2 diminished H2O2-triggered LMP, as evidenced by a reduction in acridine orange staining and leakage of cathepsin D from the lysosome to the cytoplasm. In addition, V-ATPase B2-overexpressing macrophages exhibited significantly enhanced uptake and degradation of collagen. V-ATPase B2-overexpressing transgenic mice showed significant inhibition of the bleomycin-induced increases in lung inflammation and fibrosis. We conclude that V-ATPase B2 is critical for maintaining lysosomal activities against excessive oxidative stress by stabilizing LMP. Our findings reveal a previously unknown role of this V-ATPase subunit in a lung injury and fibrosis model. |
