Cited 119 times in
PGC-1α Protects from Notch-Induced Kidney Fibrosis Development
DC Field | Value | Language |
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dc.contributor.author | 강신욱 | - |
dc.contributor.author | 박정탁 | - |
dc.contributor.author | 유태현 | - |
dc.contributor.author | 한승혁 | - |
dc.date.accessioned | 2018-07-20T08:32:42Z | - |
dc.date.available | 2018-07-20T08:32:42Z | - |
dc.date.issued | 2017 | - |
dc.identifier.issn | 1046-6673 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/161274 | - |
dc.description.abstract | Kidney fibrosis is the histologic manifestation of CKD. Sustained activation of developmental pathways, such as Notch, in tubule epithelial cells has been shown to have a key role in fibrosis development. The molecular mechanism of Notch-induced fibrosis, however, remains poorly understood. Here, we show that, that expression of peroxisomal proliferation g-coactivator (PGC-1α) and fatty acid oxidation-related genes are lower in mice expressing active Notch1 in tubular epithelial cells (Pax8-rtTA/ICN1) compared to littermate controls. Chromatin immunoprecipitation assays revealed that the Notch target gene Hes1 directly binds to the regulatory region of PGC-1α Compared with Pax8-rtTA/ICN1 transgenic animals, Pax8-rtTA/ICN1/Ppargc1a transgenic mice showed improvement of renal structural alterations (on histology) and molecular defect (expression of profibrotic genes). Overexpression of PGC-1α restored mitochondrial content and reversed the fatty acid oxidation defect induced by Notch overexpression in vitro in tubule cells. Furthermore, compared with Pax8-rtTA/ICN1 mice, Pax8-rtTA/ICN1/Ppargc1a mice exhibited improvement in renal fatty acid oxidation gene expression and apoptosis. Our results show that metabolic dysregulation has a key role in kidney fibrosis induced by sustained activation of the Notch developmental pathway and can be ameliorated by PGC-1α. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | American Society of Nephrology | - |
dc.relation.isPartOf | JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Fibrosis/etiology | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Kidney/pathology* | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/physiology* | - |
dc.subject.MESH | Receptor, Notch1/physiology* | - |
dc.subject.MESH | Receptors, Notch/physiology* | - |
dc.subject.MESH | Transcription Factors/physiology* | - |
dc.title | PGC-1α Protects from Notch-Induced Kidney Fibrosis Development | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine | - |
dc.contributor.department | Dept. of Internal Medicine | - |
dc.contributor.googleauthor | Seung Hyeok Han | - |
dc.contributor.googleauthor | Mei-yan Wu | - |
dc.contributor.googleauthor | Bo Young Nam | - |
dc.contributor.googleauthor | Jung Tak Park | - |
dc.contributor.googleauthor | Tae-Hyun Yoo | - |
dc.contributor.googleauthor | Shin-Wook Kang | - |
dc.contributor.googleauthor | Jihwan Park | - |
dc.contributor.googleauthor | Frank Chinga | - |
dc.contributor.googleauthor | Szu-Yuan Li | - |
dc.contributor.googleauthor | Katalin Susztak | - |
dc.identifier.doi | 10.1681/ASN.2017020130 | - |
dc.contributor.localId | A00053 | - |
dc.contributor.localId | A01654 | - |
dc.contributor.localId | A02526 | - |
dc.contributor.localId | A04304 | - |
dc.relation.journalcode | J01779 | - |
dc.identifier.eissn | 1533-3450 | - |
dc.identifier.pmid | 28751525 | - |
dc.identifier.url | http://jasn.asnjournals.org/content/28/11/3312.long | - |
dc.subject.keyword | Notch | - |
dc.subject.keyword | PGC-1α | - |
dc.subject.keyword | fatty acid oxidation | - |
dc.subject.keyword | kidney fibrosis | - |
dc.subject.keyword | mitochondria | - |
dc.contributor.alternativeName | Kang, Shin Wook | - |
dc.contributor.alternativeName | Park, Jung Tak | - |
dc.contributor.alternativeName | Yoo, Tae Hyun | - |
dc.contributor.alternativeName | Han, Seung Hyeok | - |
dc.contributor.affiliatedAuthor | Kang, Shin Wook | - |
dc.contributor.affiliatedAuthor | Park, Jung Tak | - |
dc.contributor.affiliatedAuthor | Yoo, Tae Hyun | - |
dc.contributor.affiliatedAuthor | Han, Seung Hyeok | - |
dc.citation.volume | 28 | - |
dc.citation.number | 11 | - |
dc.citation.startPage | 3312 | - |
dc.citation.endPage | 3322 | - |
dc.identifier.bibliographicCitation | JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, Vol.28(11) : 3312-3322, 2017 | - |
dc.identifier.rimsid | 61196 | - |
dc.type.rims | ART | - |
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