An imbalance between matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase-2 contributes to the development of early diabetic nephropathy
DC Field | Value | Language |
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dc.contributor.author | Han, Sang Youb | - |
dc.contributor.author | Jee, Yi Hwa | - |
dc.contributor.author | Han, Kum Hyun | - |
dc.contributor.author | Kang, Young Sun | - |
dc.contributor.author | Kim, Hyoung Kyu | - |
dc.contributor.author | Han, Jee Young | - |
dc.contributor.author | Kim, Young Sik | - |
dc.contributor.author | Cha, Dae Ryong | - |
dc.date.accessioned | 2021-09-09T12:14:26Z | - |
dc.date.available | 2021-09-09T12:14:26Z | - |
dc.date.created | 2021-06-18 | - |
dc.date.issued | 2006-09 | - |
dc.identifier.issn | 0931-0509 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/124290 | - |
dc.description.abstract | Background. High glucose and angiotensin-II (Ang-II) levels are the known important mediators of diabetic nephropathy. However, the effects of these mediators on matrix metalloproteinase-2 (MMP-2) and on tissue inhibitor of metalloproteinase-2 (TIMP-2) in proximal tubule cells have yet to be fully examined within the context of early stage diabetic nephropathy. Methods. In this study, we attempted to characterize changes in MMP-2 and TIMP-2 in streptozotocin-induced diabetic rats. To further examine the molecular mechanisms involved, we evaluated the effects of high glucose (30 mM) or Ang-II on MMP-2, TIMP-2 and collagen synthesis in proximal tubule cells, and investigated whether MMP-2 and TIMP-2 are regulated via the TGF-beta 1 pathway. Results. In streptozotocin-induced diabetic rats, TIMP-2 mRNA and protein levels were significantly higher than in controls. Urinary protein excretion also showed a significant positive correlation with glomerular and tubular TIMP-2 protein expressions, and a negative correlation with MMP-2 expression. In cultured cells, both high glucose and Ang-II induced significant increases in TGF-beta 1, TIMP-2, and in collagen synthesis, and significant decreases in MMP-2 gene expression and activity, and thus disrupted the balance between MMP-2 and TIMP-2. Moreover, treatment with a selective angiotensin type 1 (AT1) receptor antagonist significantly inhibited Ang-II mediated changes in TGF-beta 1, MMP-2, TIMP-2, and in collagen production, suggesting the role of the AT1 receptor. The addition of exogenous TGF-beta 1 produced an effect similar to those of high glucose and Ang-II. Furthermore, the inhibition of TGF-beta 1 protein prevented Ang-II-induced MMP-2 and TIMP-2 alterations, suggesting the involvement of a TGF-beta 1 pathway. Conclusions. High glucose or Ang-II treatment induce alterations in MMP-2 and TIMP-2 balance, which favour TIMP-2 over-activity. Moreover, Ang-II-mediated changes in the productions of MMP-2 and TIMP-2 occur via AT1 receptors and a TGF-beta 1-dependent mechanism. These results suggest that an imbalance between the MMP-2 and TIMP-2, caused primarily by an increase in TIMP-2 activity, contributes to the pathogenesis of diabetic nephropathy. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | OXFORD UNIV PRESS | - |
dc.subject | TUBULAR CELLS | - |
dc.subject | HIGH GLUCOSE | - |
dc.subject | DEGRADATION | - |
dc.subject | EXPRESSION | - |
dc.subject | COLLAGEN | - |
dc.subject | KIDNEY | - |
dc.subject | MMP-9 | - |
dc.title | An imbalance between matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase-2 contributes to the development of early diabetic nephropathy | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Cha, Dae Ryong | - |
dc.identifier.doi | 10.1093/ndt/gfl238 | - |
dc.identifier.scopusid | 2-s2.0-33750121618 | - |
dc.identifier.wosid | 000240694200014 | - |
dc.identifier.bibliographicCitation | NEPHROLOGY DIALYSIS TRANSPLANTATION, v.21, no.9, pp.2406 - 2416 | - |
dc.relation.isPartOf | NEPHROLOGY DIALYSIS TRANSPLANTATION | - |
dc.citation.title | NEPHROLOGY DIALYSIS TRANSPLANTATION | - |
dc.citation.volume | 21 | - |
dc.citation.number | 9 | - |
dc.citation.startPage | 2406 | - |
dc.citation.endPage | 2416 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Transplantation | - |
dc.relation.journalResearchArea | Urology & Nephrology | - |
dc.relation.journalWebOfScienceCategory | Transplantation | - |
dc.relation.journalWebOfScienceCategory | Urology & Nephrology | - |
dc.subject.keywordPlus | TUBULAR CELLS | - |
dc.subject.keywordPlus | HIGH GLUCOSE | - |
dc.subject.keywordPlus | DEGRADATION | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | COLLAGEN | - |
dc.subject.keywordPlus | KIDNEY | - |
dc.subject.keywordPlus | MMP-9 | - |
dc.subject.keywordAuthor | angiotensin II | - |
dc.subject.keywordAuthor | diabetic nephropathy | - |
dc.subject.keywordAuthor | high glucose | - |
dc.subject.keywordAuthor | matrix metalloproteinase-2 | - |
dc.subject.keywordAuthor | proximal tubule cell | - |
dc.subject.keywordAuthor | tissue inhibitor of matrix metalloproteinase-2 | - |
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