Overexpression of V-ATPase B2 attenuates lung injury/fibrosis by stabilizing lysosomal membrane permeabilization and increasing collagen degradation.

ABSTRACT: 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. Overexpressio

SUBMITTER: Lee JU 

PROVIDER: S-EPMC9166714 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature