Angiotensin II-mediated MYH9 downregulation causes structural and functional podocyte injury in diabetic kidney disease
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kang, Jeong Suk | - |
dc.contributor.author | Lee, Seung Joo | - |
dc.contributor.author | Lee, Ji-Hye | - |
dc.contributor.author | Kim, Ji-Hee | - |
dc.contributor.author | Son, Seung Seob | - |
dc.contributor.author | Cha, Seung-Kuy | - |
dc.contributor.author | Lee, Eun Soo | - |
dc.contributor.author | Chung, Choon Hee | - |
dc.contributor.author | Lee, Eun Young | - |
dc.date.accessioned | 2021-08-11T09:44:00Z | - |
dc.date.available | 2021-08-11T09:44:00Z | - |
dc.date.issued | 2019-05-22 | - |
dc.identifier.issn | 2045-2322 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/4525 | - |
dc.description.abstract | MYH9, a widely expressed gene encoding nonmuscle myosin heavy chain, is also expressed in podocytes and is associated with glomerular pathophysiology. However, the mechanisms underlying MYH9-related glomerular diseases associated with proteinuria are poorly understood. Therefore, we investigated the role and mechanism of MYH9 in diabetic kidney injury. MYH9 expression was decreased in glomeruli from diabetic patients and animals and in podocytes treated with Ang II in vitro. Ang II treatment and siRNA-mediated MYH9 knockdown in podocytes resulted in actin cytoskeleton reorganization, reduced cell adhesion, actin-associated protein downregulation, and increased albumin permeability. Ang II treatment increased NOX4 expression and ROS generation. The Ang II receptor blocker losartan and the ROS scavenger NAC restored MYH9 expression in Ang II-treated podocytes, attenuated disrupted actin cytoskeleton and decreased albumin permeability. Furthermore, MYH9 overexpression in podocytes restored the effects of Ang II on the actin cytoskeleton and actin-associated proteins. Ang II-mediated TRPC6 activation reduced MYH9 expression. These results suggest that Ang II-mediated MYH9 depletion in diabetic nephropathy may increase filtration barrier permeability by inducing structural and functional podocyte injury through TRPC6-mediated Ca2+ influx by NOX4-mediated ROS generation. These findings reveal a novel MYH9 function in maintaining urinary filtration barrier integrity. MYH9 may be a potential target for treating diabetic nephropathy. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Nature Publishing Group | - |
dc.title | Angiotensin II-mediated MYH9 downregulation causes structural and functional podocyte injury in diabetic kidney disease | - |
dc.type | Article | - |
dc.publisher.location | 영국 | - |
dc.identifier.doi | 10.1038/s41598-019-44194-3 | - |
dc.identifier.scopusid | 2-s2.0-85066115352 | - |
dc.identifier.wosid | 000468600100005 | - |
dc.identifier.bibliographicCitation | Scientific Reports, v.9 | - |
dc.citation.title | Scientific Reports | - |
dc.citation.volume | 9 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | NONMUSCLE MYOSIN IIA | - |
dc.subject.keywordPlus | GLOMERULAR PROTEIN | - |
dc.subject.keywordPlus | RENAL-DISEASE | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | MUTATIONS | - |
dc.subject.keywordPlus | ACTIN | - |
dc.subject.keywordPlus | GENE | - |
dc.subject.keywordPlus | TRPC6 | - |
dc.subject.keywordPlus | ASSOCIATIONS | - |
dc.subject.keywordPlus | CYTOSKELETON | - |
dc.subject.keywordAuthor | MYH9 | - |
dc.subject.keywordAuthor | Ang II | - |
dc.subject.keywordAuthor | Podocytes | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
(31538) 22, Soonchunhyang-ro, Asan-si, Chungcheongnam-do, Republic of Korea+82-41-530-1114
COPYRIGHT 2021 by SOONCHUNHYANG UNIVERSITY ALL RIGHTS RESERVED.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.