LncRNA LINC00968 accelerates the proliferation and fibrosis of diabetic nephropathy by epigenetically repressing p21 via recruiting EZH2
LncRNA LINC00968 accelerates the proliferation and fibrosis of diabetic nephropathy by epigenetically repressing p21 via recruiting EZH2
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DOI：
10.1016/j.bbrc.2018.08.048
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发表时间：
2018-10-02
影响因子：
3.1
通讯作者：
Yu, Pei
中科院分区：
文献类型：
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作者：
Li, Zhenjin;Yu, Zhiqiang;Yu, Pei
越来越多的证据表明，长链非编码rna （IncRNAs）在糖尿病肾病的病理生理过程中起着至关重要的作用。然而，IncRNAs调控糖尿病肾病发病机制的深入机制尚不清楚。在本研究中，我们发现IncRNA LINC00968在糖尿病db/db小鼠组织和高糖诱导的系膜细胞中高表达。功能实验表明，sirna沉默LINC00968可显著抑制高糖诱导的系膜细胞增殖和周期进展，降低细胞外基质（ECM）蛋白（纤连蛋白、胶原IV）表达。RNA免疫沉淀（RIP）和染色质免疫沉淀（ChIP）实验显示，LINC00968将EZH2招募到p21的启动子上，抑制其表达。综上所述，我们的研究结果支持IncRNA LINC00968通过募集EZH2通过表观遗传抑制p21加速系膜细胞增殖和纤维化的结论，为糖尿病肾病的发病机制提供了新的见解。(C) 2018爱思唯尔公司版权所有。
Emerging evidence have indicated the vital roles of long noncoding RNAs (IncRNAs) in the pathophysiological process of diabetic nephropathy. However, the deepgoing mechanism that IncRNAs regulate the diabetic nephropathy pathogenesis is still ambiguous. In present study, we found that IncRNA LINC00968 expression was high-expressed in the diabetic db/db mouse tissue and high-glucose induced mesangial cells. Functional experiments indicated that LINC00968 silencing by siRNAs significantly inhibited the proliferation and cycle progression, and decreased the extracellular matrix (ECM) proteins (fibronectin, collagen IV) expression in the high glucose induced of mesangial cells. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assay revealed that LINC00968 recruit EZH2 to the promoter of p21 to inhibit its expression. In summary, our results support the conclusion that IncRNA LINC00968 accelerates the proliferation and fibrosis of mesangial cells by epigenetically repressing p21 via recruiting EZH2, providing a novel insight for the diabetic nephropathy pathogenesis. (C) 2018 Elsevier Inc. All rights reserved.