Cited 75 times in
Repression of let-7 by transforming growth factor-β1-induced Lin28 upregulates collagen expression in glomerular mesangial cells under diabetic conditions
DC Field | Value | Language |
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dc.contributor.author | 강신욱 | - |
dc.contributor.author | 박정탁 | - |
dc.date.accessioned | 2015-12-28T11:14:29Z | - |
dc.date.available | 2015-12-28T11:14:29Z | - |
dc.date.issued | 2014 | - |
dc.identifier.issn | 1931-857X | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/139008 | - |
dc.description.abstract | Accumulation of mesangial extracellular matrix (ECM) proteins such as collagen type 1-α2 (Col1a2) and collagen type 4-α1 (Col4a1) is a key feature of diabetic nephropathy (DN). Transforming growth factor (TGF)-β1 plays important roles in ECM accumulation in DN, and evidence shows a mediatory role for microRNAs. In the present study, we found that microRNA let-7 family members (let-7b/c/d/g/i) were downregulated in TGF-β-treated mouse mesangial cells (MMCs) along with upregulation of Col1a2 and Col4a1. Ectopic expression of let-7b in TGF-β-treated MMCs attenuated Col1a2 and Col4a1 upregulation. Conversely, let-7b inhibitors increased Col1a2 and Col4a1 levels. Cotransfection of MMCs with mouse Col1a2 or Col4a1 3'-untranslated region luciferase constructs and let-7b inhibitors increased luciferase activity. However, constructs with let-7 target site mutations were unresponsive to TGF-β. TGF-β-induced 3'-untranslated region activity was attenuated by let-7b mimics, suggesting that Col1a2 and Col4a1 are direct targets of let-7b. In addition, Lin28b, a negative regulator of let-7 biogenesis, was upregulated in TGF-β-treated MMCs. Luciferase assays showed that the Lin28b promoter containing the Smad-binding element (SBE) responded to TGF-β, which was abolished in constructs without SBE. Chromatin immunoprecipitation assays showed TGF-β-induced enrichment of Smad2/3 at the Lin28b promoter, together suggesting that Lin28b is transcriptionally induced by TGF-β through SBE. Furthermore, let-7b levels were decreased, whereas Lin28b, Col1a2, and Col4a1 levels were increased, in glomeruli of diabetic mice compared with nondiabetic control mice, demonstrating the in vivo relevance of this Lin28/let-7/collagen axis. These results identify Lin28 as a new TGF-β target gene and suggest a novel role for the Lin28/let-7 pathway in controlling TGF-β-induced collagen accumulation in DN. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | F1390~F1403 | - |
dc.relation.isPartOf | AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | 3' Untranslated Regions | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Binding Sites | - |
dc.subject.MESH | Cells, Cultured | - |
dc.subject.MESH | Collagen Type I/metabolism* | - |
dc.subject.MESH | Collagen Type IV/metabolism* | - |
dc.subject.MESH | Diabetes Mellitus, Experimental/chemically induced | - |
dc.subject.MESH | Diabetes Mellitus, Experimental/genetics | - |
dc.subject.MESH | Diabetes Mellitus, Experimental/metabolism* | - |
dc.subject.MESH | Diabetes Mellitus, Experimental/pathology | - |
dc.subject.MESH | Diabetes Mellitus, Type 2/genetics | - |
dc.subject.MESH | Diabetes Mellitus, Type 2/metabolism* | - |
dc.subject.MESH | Diabetes Mellitus, Type 2/pathology | - |
dc.subject.MESH | Diabetic Nephropathies/genetics | - |
dc.subject.MESH | Diabetic Nephropathies/metabolism* | - |
dc.subject.MESH | Diabetic Nephropathies/pathology | - |
dc.subject.MESH | Dose-Response Relationship, Drug | - |
dc.subject.MESH | Down-Regulation | - |
dc.subject.MESH | Fibrosis | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Mesangial Cells/drug effects* | - |
dc.subject.MESH | Mesangial Cells/metabolism | - |
dc.subject.MESH | Mesangial Cells/pathology | - |
dc.subject.MESH | Mice, Inbred C57BL | - |
dc.subject.MESH | MicroRNAs/genetics | - |
dc.subject.MESH | MicroRNAs/metabolism* | - |
dc.subject.MESH | Mutation | - |
dc.subject.MESH | RNA Interference | - |
dc.subject.MESH | RNA-Binding Proteins/genetics | - |
dc.subject.MESH | RNA-Binding Proteins/metabolism* | - |
dc.subject.MESH | Recombinant Proteins/pharmacology | - |
dc.subject.MESH | Signal Transduction/drug effects | - |
dc.subject.MESH | Smad2 Protein/metabolism | - |
dc.subject.MESH | Smad3 Protein/metabolism | - |
dc.subject.MESH | Streptozocin | - |
dc.subject.MESH | Transcription, Genetic/drug effects | - |
dc.subject.MESH | Transfection | - |
dc.subject.MESH | Transforming Growth Factor beta1/pharmacology* | - |
dc.subject.MESH | Up-Regulation | - |
dc.title | Repression of let-7 by transforming growth factor-β1-induced Lin28 upregulates collagen expression in glomerular mesangial cells under diabetic conditions | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학) | - |
dc.contributor.googleauthor | Jung Tak Park | - |
dc.contributor.googleauthor | Mitsuo Kato | - |
dc.contributor.googleauthor | Linda Lanting | - |
dc.contributor.googleauthor | Nancy Castro | - |
dc.contributor.googleauthor | Bo Young Nam | - |
dc.contributor.googleauthor | Mei Wang | - |
dc.contributor.googleauthor | Shin-Wook Kang | - |
dc.contributor.googleauthor | Rama Natarajan | - |
dc.identifier.doi | 10.1152/ajprenal.00458.2014 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A00053 | - |
dc.contributor.localId | A01654 | - |
dc.relation.journalcode | J00108 | - |
dc.identifier.eissn | 1522-1466 | - |
dc.identifier.pmid | 25354942 | - |
dc.identifier.url | http://ajprenal.physiology.org/content/307/12/F1390.long | - |
dc.subject.keyword | Lin28b | - |
dc.subject.keyword | diabetic nephropathy | - |
dc.subject.keyword | let-7 | - |
dc.subject.keyword | microRNA | - |
dc.subject.keyword | transforming growth factor-β | - |
dc.contributor.alternativeName | Kang, Shin Wook | - |
dc.contributor.alternativeName | Park, Jung Tak | - |
dc.contributor.affiliatedAuthor | Kang, Shin Wook | - |
dc.contributor.affiliatedAuthor | Park, Jung Tak | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 307 | - |
dc.citation.number | 12 | - |
dc.citation.startPage | 1390 | - |
dc.citation.endPage | 1403 | - |
dc.identifier.bibliographicCitation | AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, Vol.307(12) : 1390-1403, 2014 | - |
dc.identifier.rimsid | 51235 | - |
dc.type.rims | ART | - |
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