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一种新型长链非编码RNA CYP4B1-PS1-001调节糖尿病肾病中的细胞增殖和纤维化。

A novel long non-coding RNA CYP4B1-PS1-001 regulates proliferation and fibrosis in diabetic nephropathy.

作者信息

Wang Min, Wang Suyu, Yao Di, Yan Qin, Lu Weiping

机构信息

Department of Endocrinology and Metabolism, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu 223300, PR China.

Department of Microbiology, Nanjing Medical University, Nanjing 210029, PR China.

出版信息

Mol Cell Endocrinol. 2016 May 5;426:136-45. doi: 10.1016/j.mce.2016.02.020. Epub 2016 Feb 26.

Abstract

Diabetic nephropathy is an important microvascular complication of diabetes, and the incidence of end-stage renal disease caused by it are rising annually. Long non-coding RNAs (lncRNAs) are widely regarded to associate with the occurrence and development of various diseases; however, the relationship between lncRNAs and diabetic nephropathy remains largely unknown. This work studied the effect of lncRNAs on diabetic nephropathy pathogenesis. LncRNA microarrays were initially used to detect lncRNAs with altered expression in three cases of kidney tissue from db/db mice with diabetic nephropathy. LncRNAs with differential expression (>2-fold) could be considered candidates. Particularly, CYP4B1-PS1-001 was significantly downregulated in response to early diabetic nephropathy in vitro and in vivo, while overexpression of CYP4B1-PS1-001 inhibited proliferation and fibrosis of mesangial cells. Overall, our data indicate the potential role of CYP4B1-PS1-001 in the proliferation and fibrosis of mice mesangial cells as the prominent features during early stage of diabetic nephropathy, which extend the relationship between lncRNAs and diabetic nephropathy, and may provide a potential therapeutic target and molecular biomarker for the disease.

摘要

糖尿病肾病是糖尿病重要的微血管并发症,由其导致的终末期肾病发病率逐年上升。长链非编码RNA(lncRNAs)被广泛认为与各种疾病的发生发展相关;然而,lncRNAs与糖尿病肾病之间的关系仍 largely未知。本研究探讨lncRNAs对糖尿病肾病发病机制的影响。最初利用lncRNA芯片检测3例糖尿病肾病db/db小鼠肾组织中表达改变的lncRNAs。差异表达(>2倍)的lncRNAs可被视为候选分子。特别地,CYP4B1-PS1-001在体外和体内早期糖尿病肾病中均显著下调,而CYP4B1-PS1-001的过表达抑制系膜细胞的增殖和纤维化。总体而言,我们的数据表明CYP4B1-PS1-001在小鼠系膜细胞增殖和纤维化中具有潜在作用,这是糖尿病肾病早期的突出特征,拓展了lncRNAs与糖尿病肾病之间的关系,并可能为该疾病提供潜在的治疗靶点和分子生物标志物。

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