Upregulation of mitochondrial Nox4 mediates TGF-beta-induced apoptosis in cultured mouse podocytes
DC Field | Value | Language |
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dc.contributor.author | Das, Ranjan | - |
dc.contributor.author | Xu, Shanhua | - |
dc.contributor.author | Quan, Xianglan | - |
dc.contributor.author | Tuyet Thi Nguyen | - |
dc.contributor.author | Kong, In Deok | - |
dc.contributor.author | Chung, Choon Hee | - |
dc.contributor.author | Lee, Eun Young | - |
dc.contributor.author | Cha, Seung-Kuy | - |
dc.contributor.author | Park, Kyu-Sang | - |
dc.date.accessioned | 2021-08-11T23:26:49Z | - |
dc.date.available | 2021-08-11T23:26:49Z | - |
dc.date.issued | 2014-01 | - |
dc.identifier.issn | 1931-857X | - |
dc.identifier.issn | 1522-1466 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/12565 | - |
dc.description.abstract | Injury to podocytes leads to the onset of chronic renal diseases characterized by proteinuria. Elevated transforming growth factor (TGF)-beta in kidney tissue is associated with podocyte damage that ultimately results in apoptosis and detachment. We investigated the proapoptotic mechanism of TGF-beta in immortalized mouse podocytes. Exogenous TGF-beta(1)-induced podocyte apoptosis through caspase-3 activation, which was related to elevated ROS levels generated by selective upregulation of NADPH oxidase 4 (Nox4). In mouse podocytes, Nox4 was predominantly localized to mitochondria, and Nox4 upregulation by TGF-beta(1) markedly depolarized mitochondrial membrane potential. TGF-beta(1)-induced ROS production and caspase activation were mitigated by an antioxidant, the Nox inhibitor diphenyleneiodonium, or small interfering RNA for Nox4. A TGF-beta receptor I blocker, SB-431542, completely reversed the changes triggered by TGF-beta(1). Knockdown of either Smad2 or Smad3 prevented the increase of Nox4 expression, ROS generation, loss of mitochondrial membrane potential, and caspase-3 activation by TGF-beta(1). These results suggest that TGF-beta(1)-induced mitochondrial Nox4 upregulation via the TGF-beta receptor-Smad2/3 pathway is responsible for ROS production, mitochondrial dysfunction, and apoptosis, which may at least in part contribute to the development and progression of proteinuric glomerular diseases such as diabetic nephropathy. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | American Physiological Society | - |
dc.title | Upregulation of mitochondrial Nox4 mediates TGF-beta-induced apoptosis in cultured mouse podocytes | - |
dc.type | Article | - |
dc.publisher.location | 미국 | - |
dc.identifier.doi | 10.1152/ajprenal.00438.2013 | - |
dc.identifier.scopusid | 2-s2.0-84892616097 | - |
dc.identifier.wosid | 000329860000002 | - |
dc.identifier.bibliographicCitation | American Journal of Physiology - Renal Physiology, v.306, no.2, pp F155 - F167 | - |
dc.citation.title | American Journal of Physiology - Renal Physiology | - |
dc.citation.volume | 306 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | F155 | - |
dc.citation.endPage | F167 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Physiology | - |
dc.relation.journalResearchArea | Urology & Nephrology | - |
dc.relation.journalWebOfScienceCategory | Physiology | - |
dc.relation.journalWebOfScienceCategory | Urology & Nephrology | - |
dc.subject.keywordPlus | GROWTH-FACTOR-BETA | - |
dc.subject.keywordPlus | TO-MESENCHYMAL TRANSITION | - |
dc.subject.keywordPlus | DIABETIC-NEPHROPATHY | - |
dc.subject.keywordPlus | NADPH OXIDASES | - |
dc.subject.keywordPlus | HIGH GLUCOSE | - |
dc.subject.keywordPlus | ENDOTHELIAL-CELLS | - |
dc.subject.keywordPlus | CARDIAC MYOCYTES | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | GLOMERULAR CELLS | - |
dc.subject.keywordPlus | COLLAGEN-IV | - |
dc.subject.keywordAuthor | podocyte | - |
dc.subject.keywordAuthor | transforming growth factor-beta | - |
dc.subject.keywordAuthor | NADPH oxidase 4 | - |
dc.subject.keywordAuthor | mitochondria | - |
dc.subject.keywordAuthor | apoptosis | - |
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