Overexpression of V-ATPase B2 attenuates lung injury/fibrosis by stabilizing lysosomal membrane permeabilization and increasing collagen degradationopen access
- Authors
- Lee, Jong-Uk; Hong, Jisu; Shin, Hyesun; Ryu, Chnag-Beom; Park, Sung-Woo; Jeong, Sung Hwan
- Issue Date
- May-2022
- Publisher
- 생화학분자생물학회
- Citation
- Experimental and Molecular Medicine, v.54, no.5, pp.662 - 672
- Journal Title
- Experimental and Molecular Medicine
- Volume
- 54
- Number
- 5
- Start Page
- 662
- End Page
- 672
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/84621
- DOI
- 10.1038/s12276-022-00776-2
- ISSN
- 1226-3613
- Abstract
- Excessive oxidative stress causes lysosomal membrane permeabilization (LMP), which leads to cell death. Vacuolar ATPase (VATPase) 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.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 의과대학 > 의학과 > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.