Cited 53 times in
Positive feedback loop between plasminogen activator inhibitor-1 and transforming growth factor-beta1 during renal fibrosis in diabetes
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 김유선 | - |
dc.date.accessioned | 2015-04-24T17:29:34Z | - |
dc.date.available | 2015-04-24T17:29:34Z | - |
dc.date.issued | 2009 | - |
dc.identifier.issn | 0250-8095 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/105501 | - |
dc.description.abstract | BACKGROUND/AIMS: Plasminogen activator inhibitor (PAI)-1 is increasingly recognized as a profibrotic factor but the mechanisms are not entirely clear. The present study examined the profibrotic mechanism of PAI-1 focusing on its effect on transforming growth factor (TGF)-beta1 in experimental diabetes. METHODS: PAI-1 knockout (KO) mesangial cells cultured under high glucose (HG) in addition to streptozotocin-induced diabetic PAI-1 KO mice were used. RESULTS: PAI-1 deficiency did not affect plasma glucose significantly but reduced the fractional mesangial area, fibronectin and collagen I expression in the renal cortex after 20 weeks of diabetes as well as in HG-stimulated mesangial cells along with suppression of TGF-beta1 mRNA expression. PAI-1 deficiency also reduced HG-induced betaig-h3, a TGF-beta1-induced gene product, mRNA expression. All these losses-of-function in PAI-1 KO mesangial cells were effectively gained by recombinant PAI-1. Recombinant PAI-1-induced fibronectin and collagen I expression was abrogated by TGF-beta1 receptor inhibitor or anti-TGF-beta antibody suggesting that the effect of PAI-1 was mediated by TGF-beta1. In a similar context, recombinant PAI-1 stimulated TGF-beta1 promoter activity to the same extent as TGF-beta1 itself. CONCLUSION: Since TGF-beta1 is well known to stimulate the PAI-1 promoter, we suggest that TGF-beta1 and PAI-1 together constitute a positive feedback loop in the development of renal fibrosis in diabetes. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 481~490 | - |
dc.relation.isPartOf | AMERICAN JOURNAL OF NEPHROLOGY | - |
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 | Animals | - |
dc.subject.MESH | Blood Glucose/metabolism | - |
dc.subject.MESH | Cell Line, Transformed | - |
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/metabolism* | - |
dc.subject.MESH | Diabetes Mellitus, Experimental/pathology | - |
dc.subject.MESH | Diabetes Mellitus, Experimental/physiopathology | - |
dc.subject.MESH | Diabetic Nephropathies/metabolism* | - |
dc.subject.MESH | Diabetic Nephropathies/pathology | - |
dc.subject.MESH | Diabetic Nephropathies/physiopathology | - |
dc.subject.MESH | Feedback, Physiological/physiology* | - |
dc.subject.MESH | Fibrinolysin/metabolism | - |
dc.subject.MESH | Fibronectins/metabolism | - |
dc.subject.MESH | Fibrosis | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Matrix Metalloproteinase 9/metabolism | - |
dc.subject.MESH | Mesangial Cells/metabolism | - |
dc.subject.MESH | Mesangial Cells/pathology | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Inbred C57BL | - |
dc.subject.MESH | Mice, Knockout | - |
dc.subject.MESH | Osmotic Pressure/physiology | - |
dc.subject.MESH | Promoter Regions, Genetic/physiology | - |
dc.subject.MESH | Proteinuria/metabolism | - |
dc.subject.MESH | Proteinuria/pathology | - |
dc.subject.MESH | Proteinuria/physiopathology | - |
dc.subject.MESH | RNA, Messenger/metabolism | - |
dc.subject.MESH | Serpin E2 | - |
dc.subject.MESH | Serpins/genetics | - |
dc.subject.MESH | Serpins/metabolism* | - |
dc.subject.MESH | Transforming Growth Factor beta1/genetics | - |
dc.subject.MESH | Transforming Growth Factor beta1/metabolism* | - |
dc.title | Positive feedback loop between plasminogen activator inhibitor-1 and transforming growth factor-beta1 during renal fibrosis in diabetes | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Surgery (외과학) | - |
dc.contributor.googleauthor | Ji Yeon Seo | - |
dc.contributor.googleauthor | Jehyun Park | - |
dc.contributor.googleauthor | Mi Ra Yu | - |
dc.contributor.googleauthor | Yu Seun Kim | - |
dc.contributor.googleauthor | Hunjoo Ha | - |
dc.contributor.googleauthor | Hi Bahl Lee | - |
dc.identifier.doi | 10.1159/000242477 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A00785 | - |
dc.relation.journalcode | J00094 | - |
dc.identifier.eissn | 1421-9670 | - |
dc.identifier.pmid | 19786738 | - |
dc.identifier.url | http://www.karger.com/Article/FullText/242477 | - |
dc.subject.keyword | βig-h3 | - |
dc.subject.keyword | Diabetic nephropathy | - |
dc.subject.keyword | Knockout mice | - |
dc.subject.keyword | Matrix metalloproteinase | - |
dc.subject.keyword | Mesangial cells | - |
dc.subject.keyword | Plasmin | - |
dc.subject.keyword | Plasminogen activator inhibitor-1 | - |
dc.subject.keyword | Renal fibrosis | - |
dc.subject.keyword | Transforming growth factor- β1 | - |
dc.contributor.alternativeName | Kim, Yu Seun | - |
dc.contributor.affiliatedAuthor | Kim, Yu Seun | - |
dc.citation.volume | 30 | - |
dc.citation.number | 6 | - |
dc.citation.startPage | 481 | - |
dc.citation.endPage | 490 | - |
dc.identifier.bibliographicCitation | AMERICAN JOURNAL OF NEPHROLOGY, Vol.30(6) : 481-490, 2009 | - |
dc.identifier.rimsid | 44311 | - |
dc.type.rims | ART | - |
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