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学科主题: 基础医学
题名:
Liver X receptor agonist TO-901317 upregulates SCD1 expression in renal proximal straight tubule
作者: Zhang, YH; Zhang, XY; Chen, LH; Wu, J; Su, DM; Lu, WJ; Hwang, MT; Yang, GR; Li, S; Wei, MF; Davis, L; Breyer, MD; Guan, YF
关键词: gene expression ; stearoyl-coenzyme A desaturase-1 ; sterol regulatory element binding protein-1 ; lipid metabolism
刊名: AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
发表日期: 2006-05-01
DOI: 10.1152/ajprenal.00131.2005
卷: 290, 期:5, 页:F1065-F1073
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Physiology ; Urology & Nephrology
研究领域[WOS]: Physiology ; Urology & Nephrology
关键词[WOS]: STEAROYL-COA DESATURASE-1 ; BINDING PROTEIN-1C GENE ; CHOLESTEROL EFFLUX ; LIPID-METABOLISM ; NUCLEAR RECEPTORS ; ACID-METABOLISM ; MESANGIAL CELLS ; SREBP PATHWAY ; LXR-ALPHA ; MICE
英文摘要:

Liver X receptors (LXRs), including LXR alpha and LXR beta, are intracellular sterol sensors that regulate expression of genes controlling fatty acid and cholesterol absorption, excretion, catabolism, and cellular efflux. Because the kidney plays an important role in lipid metabolism and dyslipidemia accelerates renal damage, we investigated the effect of TO-901317, an LXR agonist, on the gene expression profile in mouse kidney. Treatment of C57 Bl/6 mice with TO-901317 ( 3 mg . kg(-1) . day(-1)) for 3 days resulted in 51 transcripts that were significantly regulated in the kidney. Among them, the stearoyl-CoA desaturase-1 (SCD1) was upregulated most dramatically. Northern blot analysis revealed that SCD1 mRNA levels were markedly higher than that in control kidneys. Enhanced SCD1 expression by TO-901317 also resulted in increased fatty acid desaturation in the kidney. In control mice, constitutive renal SCD1 expression was low; however, TO-901317 treatment markedly increased SCD1 expression in the outer stripe of the outer medulla as assessed by both in situ hybridization and immunostain. Double-labeling studies further indicated that SCD1 mRNA was selectively expressed in proximal straight tubules negative for aquaporin-2 and Tamm-Horsfall protein. In vitro studies in cultured murine proximal tubule cells further demonstrated that LXR activation enhanced SCD1 transcription via increased sterol regulatory element binding protein-1. Taken together, these data suggest LXR activation of SCD1 expression may play an important role in regulating lipid metabolism and cell function in renal proximal straight tubules.

语种: 英语
WOS记录号: WOS:000236601000013
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62133
Appears in Collections:基础医学院_北京大学糖尿病中心_期刊论文

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作者单位: 1.Vanderbilt Univ, Med Ctr, Dept Med, Div Nephrol, Nashville, TN 37232 USA
2.Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Ctr Diabet, Beijing 100871, Peoples R China

Recommended Citation:
Zhang, YH,Zhang, XY,Chen, LH,et al. Liver X receptor agonist TO-901317 upregulates SCD1 expression in renal proximal straight tubule[J]. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY,2006,290(5):F1065-F1073.
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