Cited 69 times in
Role of 12-lipoxygenase in the stimulation of p38 MAPK and collagen alpha5(IV) in experimental diabetic nephropathy and in glucose-stimulated podocyte
DC Field | Value | Language |
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dc.contributor.author | 강신욱 | - |
dc.date.accessioned | 2015-07-15T17:06:09Z | - |
dc.date.available | 2015-07-15T17:06:09Z | - |
dc.date.issued | 2003 | - |
dc.identifier.issn | 1046-6673 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/114230 | - |
dc.description.abstract | The 12-lipoxygenase (12-LO) pathway of arachidonic acid metabolism is implicated in extracellular matrix (ECM) synthesis, but its role in podocytes has not been studied. This study tested whether 12-LO induction by diabetes or by high glucose (HG) in cultured podocytes alters glomerular basement membrane by activating signal transduction pathways culminating in ECM synthesis. Sprague-Dawley rats received an injection of diluent (control [C]) or streptozotocin 65 mg/kg (DM) and were killed at 1 or 4 mo. Glomerular 12-LO mRNA and protein levels were higher in DM than in C glomeruli at 1 and 4 mo, and 12-LO localized predominantly in podocytes. Glomerular p38 mRNA and protein were higher in DM at months 1 and 4, but phospho-p38 mitogen-activated protein (MAPK) was increased only at month 1. Glomerular collagen alpha5(IV)/glutaraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA ratio was increased in DM at month 1 but not at month 4, whereas collagen alpha5(IV) protein was higher at both 1 and 4 mo. Mouse podocytes were cultured in media with 25 mM glucose (HG) with or without the 12-LO inhibitor cinnamyl-3,4-dihydroxy-cyanocinnamate (CDC) or with 5.5 mM glucose + 19.5 mM mannitol (low glucose [LG+M]) for 10 d at 37 degrees C. 12-LO mRNA and protein levels were higher in HG than in LG+M as was the p38 MAPK/GAPDH mRNA ratio. Phospho-p38 MAPK protein but not total p38 MAPK was higher in HG compared with LG+M. Collagen alpha5(IV)/GAPDH mRNA ratio and protein were higher in HG than in LG+M. 12-LO inhibition by CDC decreased HG-induced phospho-p38 MAPK and the phospho-p38/total p38 MAPK ratio, collagen alpha5(IV)/GAPDH mRNA ratio, and collagen alpha5(IV) protein expression. In summary, diabetes in vivo and exposure of podocytes to HG in vitro stimulated 12-LO, p38 MAPK, and collagen alpha5(IV) mRNA and (activated) protein. 12-LO inhibition by CDC diminished the expression of podocyte phospho-p38 MAPK and collagen alpha5(IV) mRNA and protein. These findings implicate 12-LO and the p38 MAPK signaling pathway in the mediation of ECM synthesis by podocytes in diabetes. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 3178~3187 | - |
dc.relation.isPartOf | JOURNAL OF THE AMERICAN SOCIETY 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.title | Role of 12-lipoxygenase in the stimulation of p38 MAPK and collagen alpha5(IV) in experimental diabetic nephropathy and in glucose-stimulated podocyte | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학) | - |
dc.contributor.googleauthor | Shin-Wook Kang | - |
dc.contributor.googleauthor | Rama Natarajan | - |
dc.contributor.googleauthor | Sharon G. Adler | - |
dc.contributor.googleauthor | Clifford Kashtan | - |
dc.contributor.googleauthor | Peter Mundel | - |
dc.contributor.googleauthor | Janine LaPage | - |
dc.contributor.googleauthor | Cynthia C. Nast | - |
dc.contributor.googleauthor | Asha Shahed | - |
dc.identifier.doi | 10.1097/01.ASN.0000099702.16315.DE | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A00053 | - |
dc.relation.journalcode | J01779 | - |
dc.identifier.eissn | 1533-3450 | - |
dc.identifier.pmid | 10.1097/01.ASN.0000099702.16315.DE | - |
dc.contributor.alternativeName | Kang, Shin Wook | - |
dc.contributor.affiliatedAuthor | Kang, Shin Wook | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 14 | - |
dc.citation.number | 12 | - |
dc.citation.startPage | 3178 | - |
dc.citation.endPage | 3187 | - |
dc.identifier.bibliographicCitation | JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, Vol.14(12) : 3178-3187, 2003 | - |
dc.identifier.rimsid | 41502 | - |
dc.type.rims | ART | - |
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