Blocking lysophosphatidic acid receptor 1 signaling inhibits diabetic nephropathy in db/db mice
DC Field | Value | Language |
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dc.contributor.author | Li, Hui Ying | - |
dc.contributor.author | Oh, Yoon Sin | - |
dc.contributor.author | Choi, Ji-Woong | - |
dc.contributor.author | Jung, Ji Yong | - |
dc.contributor.author | Jun, Hee-Sook | - |
dc.date.available | 2020-02-27T18:42:23Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2017-06 | - |
dc.identifier.issn | 0085-2538 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/6047 | - |
dc.description.abstract | Lysophosphatidic acid (LPA) is known to regulate various biological responses by binding to LPA receptors. The serum level of LPA is elevated in diabetes, but the involvement of LPA in the development of diabetes and its complications remains unknown. Therefore, we studied LPA signaling in diabetic nephropathy and the molecular mechanisms involved. The expression of autotaxin, an LPA synthesis enzyme, and LPA receptor 1 was significantly increased in both mesangial cells (SV40 MES13) maintained in high-glucose media and the kidney cortex of diabetic db/db mice. Increased urinary albumin excretion, increased glomerular tuft area and volume, and mesangial matrix expansion were observed in db/db mice and reduced by treatment with ki16425, a LPA receptor 1/3 antagonist. Transforming growth factor (TGF)beta expression and Smad-2/3 phosphorylation were upregulated in SV40 MES13 cells by LPA stimulation or in the kidney cortex of db/db mice, and this was blocked by ki16425 treatment. LPA receptor 1 siRNA treatment inhibited LPA-induced TGF beta expression, whereas cells overexpressing LPA receptor 1 showed enhanced LPA-induced TGF beta expression. LPA treatment of SV40 MES13 cells increased phosphorylated glycogen synthase kinase (GSK)3 beta at Ser9 and induced translocation of sterol regulatory element-binding protein (SREBP)1 into the nucleus. Blocking GSK3 beta phosphorylation inhibited SREBP1 activation and consequently blocked LPA-induced TGF beta expression in SV40 MES13 cells. Phosphorylated GSK3 beta and nuclear SREBP1 accumulation were increased in the kidney cortex of db/db mice and ki16425 treatment blocked these pathways. Thus, LPA receptor 1 signaling increased TGF beta expression via GSK3 beta phosphorylation and SREBP1 activation, contributing to the development of diabetic nephropathy. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER SCIENCE INC | - |
dc.relation.isPartOf | KIDNEY INTERNATIONAL | - |
dc.subject | GLOMERULAR MESANGIAL CELLS | - |
dc.subject | RENAL LIPID-METABOLISM | - |
dc.subject | SYNTHASE KINASE 3-BETA | - |
dc.subject | TGF-BETA | - |
dc.subject | GENE-EXPRESSION | - |
dc.subject | ENDOTHELIAL-CELLS | - |
dc.subject | PROTEIN-SYNTHESIS | - |
dc.subject | UP-REGULATION | - |
dc.subject | MOUSE MODELS | - |
dc.subject | HIGH GLUCOSE | - |
dc.title | Blocking lysophosphatidic acid receptor 1 signaling inhibits diabetic nephropathy in db/db mice | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000402231400014 | - |
dc.identifier.doi | 10.1016/j.kint.2016.11.010 | - |
dc.identifier.bibliographicCitation | KIDNEY INTERNATIONAL, v.91, no.6, pp.1362 - 1373 | - |
dc.identifier.scopusid | 2-s2.0-85009724423 | - |
dc.citation.endPage | 1373 | - |
dc.citation.startPage | 1362 | - |
dc.citation.title | KIDNEY INTERNATIONAL | - |
dc.citation.volume | 91 | - |
dc.citation.number | 6 | - |
dc.contributor.affiliatedAuthor | Li, Hui Ying | - |
dc.contributor.affiliatedAuthor | Oh, Yoon Sin | - |
dc.contributor.affiliatedAuthor | Choi, Ji-Woong | - |
dc.contributor.affiliatedAuthor | Jung, Ji Yong | - |
dc.contributor.affiliatedAuthor | Jun, Hee-Sook | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | diabetic nephropathy | - |
dc.subject.keywordAuthor | extracellular matrix (ECM) | - |
dc.subject.keywordAuthor | lysophosphatidic acid (LPA) | - |
dc.subject.keywordAuthor | mesangial cell | - |
dc.subject.keywordAuthor | transforming growth factor-beta (TGF-beta) | - |
dc.subject.keywordPlus | GLOMERULAR MESANGIAL CELLS | - |
dc.subject.keywordPlus | RENAL LIPID-METABOLISM | - |
dc.subject.keywordPlus | SYNTHASE KINASE 3-BETA | - |
dc.subject.keywordPlus | TGF-BETA | - |
dc.subject.keywordPlus | GENE-EXPRESSION | - |
dc.subject.keywordPlus | ENDOTHELIAL-CELLS | - |
dc.subject.keywordPlus | PROTEIN-SYNTHESIS | - |
dc.subject.keywordPlus | UP-REGULATION | - |
dc.subject.keywordPlus | MOUSE MODELS | - |
dc.subject.keywordPlus | HIGH GLUCOSE | - |
dc.relation.journalResearchArea | Urology & Nephrology | - |
dc.relation.journalWebOfScienceCategory | Urology & Nephrology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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