Cited 81 times in
Transforming growth factor β1 (TGF-β1) enhances expression of profibrotic genes through a novel signaling cascade and microRNAs in renal mesangial cells
DC Field | Value | Language |
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dc.contributor.author | 박정탁 | - |
dc.date.accessioned | 2018-05-10T06:46:42Z | - |
dc.date.available | 2018-05-10T06:46:42Z | - |
dc.date.issued | 2014 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/158616 | - |
dc.description.abstract | Increased expression of transforming growth factor-β1 (TGF-β1) in glomerular mesangial cells (MC) augments extracellular matrix accumulation and hypertrophy during the progression of diabetic nephropathy (DN), a debilitating renal complication of diabetes. MicroRNAs (miRNAs) play key roles in the pathogenesis of DN by modulating the actions of TGF-β1 to enhance the expression of profibrotic genes like collagen. In this study, we found a significant decrease in the expression of miR-130b in mouse MC treated with TGF-β1. In parallel, there was a down-regulation in miR-130b host gene 2610318N02RIK (RIK), suggesting host gene-dependent expression of this miRNA. TGF-β receptor 1 (TGF-βR1) was identified as a target of miR-130b. Interestingly, the RIK promoter contains three NF-Y binding sites and was regulated by NF-YC. Furthermore, NF-YC expression was inhibited by TGF-β1, suggesting that a signaling cascade, involving TGF-β1-induced decreases in NF-YC, RIK, and miR-130b, may up-regulate TGF-βR1 to augment expression of TGF-β1 target fibrotic genes. miR-130b was down-regulated, whereas TGF-βR1, as well as the profibrotic genes collagen type IV α 1 (Col4a1), Col12a1, CTGF, and PAI-1 were up-regulated not only in mouse MC treated with TGF-β1 but also in the glomeruli of streptozotocin-injected diabetic mice, supporting in vivo relevance. Together, these results demonstrate a novel miRNA- and host gene-mediated amplifying cascade initiated by TGF-β1 that results in the up-regulation of profibrotic factors, such as TGF-βR1 and collagens associated with the progression of DN. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | American Society for Biochemistry and Molecular Biology | - |
dc.relation.isPartOf | JOURNAL OF BIOLOGICAL CHEMISTRY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | 3' Untranslated Regions | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | CCAAT-Binding Factor/metabolism | - |
dc.subject.MESH | Cells, Cultured | - |
dc.subject.MESH | Collagen Type IV/metabolism | - |
dc.subject.MESH | Diabetic Nephropathies/metabolism* | - |
dc.subject.MESH | Disease Progression | - |
dc.subject.MESH | Fibrosis | - |
dc.subject.MESH | Gene Expression Regulation* | - |
dc.subject.MESH | Kidney/metabolism | - |
dc.subject.MESH | Mesangial Cells/metabolism* | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Inbred C57BL | - |
dc.subject.MESH | MicroRNAs/metabolism* | - |
dc.subject.MESH | Protein-Serine-Threonine Kinases/metabolism* | - |
dc.subject.MESH | Receptors, Transforming Growth Factor beta/metabolism* | - |
dc.subject.MESH | Signal Transduction | - |
dc.subject.MESH | Transforming Growth Factor beta1/pharmacology* | - |
dc.title | Transforming growth factor β1 (TGF-β1) enhances expression of profibrotic genes through a novel signaling cascade and microRNAs in renal mesangial cells | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine | - |
dc.contributor.department | Dept. of Internal Medicine | - |
dc.contributor.googleauthor | Nancy E. Castro | - |
dc.contributor.googleauthor | Mitsuo Kato | - |
dc.contributor.googleauthor | Jung Tak Park | - |
dc.contributor.googleauthor | Rama Natarajan | - |
dc.identifier.doi | 10.1074/jbc.M114.600783 | - |
dc.contributor.localId | A01654 | - |
dc.relation.journalcode | J01258 | - |
dc.identifier.eissn | 1083-351X | - |
dc.identifier.pmid | 25204661 | - |
dc.subject.keyword | Collagen | - |
dc.subject.keyword | Diabetes | - |
dc.subject.keyword | Kidney | - |
dc.subject.keyword | MicroRNA (miRNA) | - |
dc.subject.keyword | Signaling | - |
dc.contributor.alternativeName | Park, Jung Tak | - |
dc.contributor.affiliatedAuthor | Park, Jung Tak | - |
dc.citation.volume | 289 | - |
dc.citation.number | 42 | - |
dc.citation.startPage | 29001 | - |
dc.citation.endPage | 29013 | - |
dc.identifier.bibliographicCitation | JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.289(42) : 29001-29013, 2014 | - |
dc.identifier.rimsid | 43194 | - |
dc.type.rims | ART | - |
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