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Expression profiling of hepatic genes associated with lipid metabolism in nephrotic rats
Zhou, Yunfeng1; Zhang, Xiaoyan1; Chen, Lihong1; Wu, Jing1; Dang, Huaixin1; Wei, Mingfen1; Fan, Yanbo2; Zhang, Yahua3; Zhu, Yi1; Wang, Nanping2; Breyer, Matthew D.3; Guan, Youfei1,3
关键词Microarrays Nephrotic Syndrome Lipid
刊名AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
2008-09-01
DOI10.1152/ajprenal.00046.2008
295期:3页:F662-F671
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Physiology ; Urology & Nephrology
资助者National Science Foundation of China ; National Institute of Diabetes and Digestive and Kidney Diseases ; National Science Foundation of China ; National Institute of Diabetes and Digestive and Kidney Diseases
研究领域[WOS]Physiology ; Urology & Nephrology
关键词[WOS]DENSITY-LIPOPROTEIN RECEPTOR ; ELEMENT-BINDING PROTEIN ; PUROMYCIN-INDUCED NEPHROSIS ; ATP-CITRATE-LYASE ; ACYL-COA ; DOWN-REGULATION ; MESSENGER-RNA ; VLDL RECEPTOR ; CHOLESTEROL-METABOLISM ; MOLECULAR-CLONING
英文摘要

Hyperlipidemia is one of the major features of nephrotic syndrome (NS). Although many factors have been implicated in the pathogenesis of NS-related dyslipidemia, the underlying mechanisms remain largely uncharacterized. The present study was designed to examine the gene profile associated with lipid metabolism in the livers of nephrotic rats. NS was created in male Sprague-Dawley rats (n = 6) receiving sequential intraperitoneal injections of puromycin aminonucleoside. Analysis by Affymetrix assay, quantitative RT-PCR, and Northern and Western blotting revealed 21 genes associated with cholesterol and fatty acid metabolism. Eight genes involved in cholesterol metabolism, Apo A-I, Acly, Acat, Mpd, Fdps, Ss, Lss, and Nsdhl, were significantly upregulated under NS. Four genes involved in fatty acid biosynthesis, Acc, FAS, ELOVL 2, and ELOVL 6, and three critical for triglyceride biosynthesis, Gpam, Agpat 3, and Dgat 1, were significantly upregulated, whereas two genes involved in fatty acid oxidation, Dci and MCAD, were downregulated. Expression of several genes in sterol-regulatory element-binding protein (SREBP)-1 activation was also aberrantly altered in nephrotic livers. The expression and transcriptional activity of SREBP-1 but not SREBP-2 were increased in nephrotic rats as assessed by real-time PCR, immunoblotting, and gel shift assays. The upregulation of hepatic genes involved in cholesterol biosynthesis may play an important role in the pathogenesis of hypercholesterolemia, whereas upregulation of genes participating in hepatic fatty acid and triglyceride biosynthesis and down-regulation of genes involved in hepatic fatty acid oxidation may contribute to hypertriglyceridemia in nephrotic rats. Activation of SREBP-1 transcription factor may represent an underlying molecular mechanism of hyperlipidemia in NS.

语种英语
所属项目编号30670766/30530340/30771030 ; RO1-DK-065074-04 ; PO1-DK-38226
资助者National Science Foundation of China ; National Institute of Diabetes and Digestive and Kidney Diseases ; National Science Foundation of China ; National Institute of Diabetes and Digestive and Kidney Diseases
WOS记录号WOS:000258876800006
引用统计
被引频次:23[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56140
专题基础医学院_心血管所
作者单位1.Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100871, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100871, Peoples R China
3.Vanderbilt Univ, Med Ctr, Div Nephrol & Hypertens, Nashville, TN USA
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Zhou, Yunfeng,Zhang, Xiaoyan,Chen, Lihong,et al. Expression profiling of hepatic genes associated with lipid metabolism in nephrotic rats[J]. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY,2008,295(3):F662-F671.
APA Zhou, Yunfeng.,Zhang, Xiaoyan.,Chen, Lihong.,Wu, Jing.,Dang, Huaixin.,...&Guan, Youfei.(2008).Expression profiling of hepatic genes associated with lipid metabolism in nephrotic rats.AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY,295(3),F662-F671.
MLA Zhou, Yunfeng,et al."Expression profiling of hepatic genes associated with lipid metabolism in nephrotic rats".AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 295.3(2008):F662-F671.
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