Wang Min, Yao Di, Wang Suyu, Yan Qin, Lu Weiping
Department of Endocrinology and Metabolism, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu, 223300, P. R. China.
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, 210029, P. R. China.
Endocrine. 2016 Oct;54(1):81-92. doi: 10.1007/s12020-016-0950-5. Epub 2016 Apr 15.
Diabetic nephropathy as the primary cause of end-stage renal disease reveals an increased incidence in patients with kidney disease as the continuous rising of type 2 diabetes. Long non-coding RNAs (lncRNAs) are involved in the development of many diseases including diabetes; however, the role of lncRNAs in diabetic nephropathy is still unclear. In the present study, lncRNA microarray analysis was used to identify abnormally expressed lncRNAs and nearby mRNAs in renal cortical tissues dissected from kidney of db/db and db/m mice. After verifying the data from microarray analysis by quantitative RT-PCR, downregulated ENSMUST00000147869 associated with Cyp4a12a was selected for overexpression in mouse mesangial cells among differentially expressed lncRNAs. Cell Counting Kit-8, Western blotting, and quantitative RT-PCR showed that proliferation and fibrosis indexes were reversed in mesangial cells with ENSMUST00000147869 overexpression. Our data suggested the potential role of ENSMUST00000147869 in proliferation and fibrosis of mesangial cells, which provided a molecular biomarker and therapeutic target for diabetic nephropathy.
作为终末期肾病的主要病因,随着2型糖尿病发病率的持续上升,糖尿病肾病在肾病患者中的发病率也在增加。长链非编码RNA(lncRNAs)参与包括糖尿病在内的多种疾病的发生发展;然而,lncRNAs在糖尿病肾病中的作用仍不清楚。在本研究中,利用lncRNA芯片分析来鉴定从db/db和db/m小鼠肾脏分离的肾皮质组织中异常表达的lncRNAs及其附近的mRNA。通过定量RT-PCR验证芯片分析数据后,在差异表达的lncRNAs中,选择与Cyp4a12a相关的下调的ENSMUST00000147869在小鼠系膜细胞中进行过表达。细胞计数试剂盒-8、蛋白质印迹法和定量RT-PCR显示,ENSMUST00000147869过表达的系膜细胞中增殖和纤维化指标得到逆转。我们的数据表明ENSMUST00000147869在系膜细胞增殖和纤维化中具有潜在作用,这为糖尿病肾病提供了一种分子生物标志物和治疗靶点。