Overexpression of V-ATPase B2 attenuates lung injury/fibrosis by stabilizing lysosomal membrane permeabilization and increasing collagen degradation
DC Field | Value | Language |
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dc.contributor.author | Lee, Jong-Uk | - |
dc.contributor.author | Hong, Jisu | - |
dc.contributor.author | Shin, Hyesun | - |
dc.contributor.author | Ryu, Chnag-Beom | - |
dc.contributor.author | Park, Sung-Woo | - |
dc.contributor.author | Jeong, Sung Hwan | - |
dc.date.accessioned | 2022-06-14T00:40:08Z | - |
dc.date.available | 2022-06-14T00:40:08Z | - |
dc.date.created | 2022-06-07 | - |
dc.date.issued | 2022-05 | - |
dc.identifier.issn | 1226-3613 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/84621 | - |
dc.description.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. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | 생화학분자생물학회 | - |
dc.relation.isPartOf | Experimental and Molecular Medicine | - |
dc.title | Overexpression of V-ATPase B2 attenuates lung injury/fibrosis by stabilizing lysosomal membrane permeabilization and increasing collagen degradation | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000805511100001 | - |
dc.identifier.doi | 10.1038/s12276-022-00776-2 | - |
dc.identifier.bibliographicCitation | Experimental and Molecular Medicine, v.54, no.5, pp.662 - 672 | - |
dc.identifier.kciid | ART002845832 | - |
dc.description.isOpenAccess | Y | - |
dc.identifier.scopusid | 2-s2.0-85130750600 | - |
dc.citation.endPage | 672 | - |
dc.citation.startPage | 662 | - |
dc.citation.title | Experimental and Molecular Medicine | - |
dc.citation.volume | 54 | - |
dc.citation.number | 5 | - |
dc.contributor.affiliatedAuthor | Jeong, Sung Hwan | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | PROTON MOTIVE FORCE | - |
dc.subject.keywordPlus | CELL-DEATH | - |
dc.subject.keywordPlus | MATRIX METALLOPROTEINASES | - |
dc.subject.keywordPlus | PHAGOCYTOSIS | - |
dc.subject.keywordPlus | TRANSPORT | - |
dc.subject.keywordPlus | PROTEINS | - |
dc.subject.keywordPlus | FIBROBLASTS | - |
dc.subject.keywordPlus | LIPOSOMES | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.subject.keywordPlus | DIGESTION | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.description.journalRegisteredClass | kci | - |
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