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学科主题: 基础医学
题名:
PPAR gamma Agonist Rosiglitazone Suppresses Renal mPGES-1/PGE2 Pathway in db/db Mice
作者: Sun, Ying1,2,3; Jia, Zhanjun2,3; Liu, Gang2,3; Zhou, Li2,3; Liu, Mi2,3; Yang, Baoxue1; Yang, Tianxin2,3,4,5
刊名: PPAR RESEARCH
发表日期: 2013
DOI: 10.1155/2013/612971
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Medicine, Research & Experimental
研究领域[WOS]: Research & Experimental Medicine
关键词[WOS]: PROSTAGLANDIN-E RECEPTORS ; DIABETIC-NEPHROPATHY ; GLYBURIDE MONOTHERAPY ; METABOLIC SYNDROME ; LEPTIN RECEPTOR ; TYPE-2 ; KIDNEY ; E-2 ; STREPTOZOTOCIN ; ALBUMINURIA
英文摘要:

Evidence had shown the detrimental effect of prostaglandin (PG) E2 in diabetic nephropathy (DN) of STZ-induced type-1 diabetes but its role in the development of DN of type-2 diabetes remains uncertain. The present study was undertaken to investigate the regulation of PGE2 synthetic pathway and the interaction between peroxisome proliferator-activated receptor (PPAR)gamma and PGE2 synthesis in the kidneys of db/db mice. Strikingly, urinary PGE2 was remarkably elevated in db/db mice paralleled with the increased protein expressions of COX-2 and mPGES-1. In contrast, the protein expressions of COX-1, mPGES-2, cPGES, and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) were not altered. Following 1-week rosiglitazone (Rosi) therapy, urinary PGE2, but not other prostanoids, was reduced by 57% in parallel with significant reduction of mPGES-1 protein and EP4 mRNA expressions. By immunohistochemistry, mPGES-1 was significantly induced in the glomeruli of db/db mice, which was almost entirely abolished by Rosi. In line with the reduction of glomerular mPGES-1, the glomerular injury score showed a tendency of improvement after 1 week of Rosi therapy. Collectively, the present study demonstrated an inhibitory effect of PPAR gamma activation on renal mPGES-1/PGE2/EP4 pathway in type-2 diabetes and suggested that mPGES-1 may potentially serve as a therapeutic target for treating type-2 diabetes-associated DN.

语种: 英语
所属项目编号: DK079162 ; 11SDG7480006
项目资助者: VA Merit Review ; National Institutes of Health
WOS记录号: WOS:000329627500001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56198
Appears in Collections:基础医学院_药理学系_期刊论文

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作者单位: 1.Vet Affairs Med Ctr, Salt Lake City, UT 84148 USA
2.Vet Affairs Med Ctr, Salt Lake City, UT 84132 USA
3.Peking Univ, Dept Pharmacol, Sch Basic Med Sci, Beijing 100191, Peoples R China
4.Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA
5.Univ Utah, Div Nephrol & Hypertens, Salt Lake City, UT 84132 USA

Recommended Citation:
Sun, Ying,Jia, Zhanjun,Liu, Gang,et al. PPAR gamma Agonist Rosiglitazone Suppresses Renal mPGES-1/PGE2 Pathway in db/db Mice[J]. PPAR RESEARCH,2013.
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