The Long Noncoding RNA 150Rik Promotes Mesangial Cell Proliferation via miR-451/IGF1R/p38 MAPK Signaling in Diabetic Nephropathy.
The Long Noncoding RNA 150Rik Promotes Mesangial Cell Proliferation via miR-451/IGF1R/p38 MAPK Signaling in Diabetic Nephropathy.
复制标题
长非编码 RNA 150Rik 通过 miR-451/IGF1R/p38 MAPK 信号传导促进糖尿病肾病的肾小球系膜细胞增殖。
DOI：
10.1159/000495590
复制
发表时间：
2018
影响因子：
--
通讯作者：
Zhang Zheng
中科院分区：
文献类型：
--
作者：
Zhang Yajuan;Sun Yan;Peng Rui;Liu H;eng;He Weihao;Zhang Luyu;Peng Huimin;Zhang Zheng
背景/目的糖尿病肾病（DN）作为终末期肾脏疾病的主要病因是糖尿病的常见并发症。然而，引发DN的起始分子事件尚不清楚。近年来，长链非编码rna （lncRNAs）在DN中发挥了重要作用。方法采用qRT-PCR （quantitative real-time PCR）检测lncRNA 1500026H17Rik（简称150Rik）的表达水平。用5-乙基-2′-脱氧尿苷（EdU）检测细胞增殖能力。采用荧光素酶法和RNA免疫沉淀（RIP）法检测150Rik与microRNA 451 （miR-451）的关系。最后，通过EdU、流式细胞术分析、western blot检测150Rik通过miR-451/胰岛素样生长因子1受体(IGF1R)/丝裂原活化蛋白激酶（p38MAPK）通路对细胞增殖的影响。结果我们发现150Rik是一种进化上保守的lncRNA，在db/db DN小鼠的肾组织和高糖条件下培养的肾小球系膜细胞（MCs）中显著上调。此外，研究发现150Rik的过表达或敲低可调节MCs中的细胞增殖。此外，150Rik被发现以直接和argonaute-2 （Ago2）依赖的方式与miR-451相互作用。结果还显示，在高糖条件下，150Rik的过表达通过miR-451/IGF1R/p38MAPK途径抑制MCs细胞增殖，而150Rik的敲低通过miR-451/IGF1R/p38MAPK途径增加细胞增殖。综上所述，这些结果为150Rik与DN进展过程中miR-451/IGF1R/p38MAPK信号通路之间的关系提供了新的见解。
Background/AimsDiabetic nephropathy (DN) as the primary cause of end-stage kidney disease is a common complication of diabetes. However, the initiating molecular events triggering DN are unknown. Recently, long noncoding RNAs (lncRNAs) have been shown to play important roles in DN.MethodsThe expression level of lncRNA 1500026H17Rik (150Rik for short) was measured by qRT-PCR (quantitative real-time PCR). Cell proliferation ability was detected by 5-Ethynyl-2’-deoxyuridine (EdU). The relationship between 150Rik and microRNA 451 (miR-451) was examined by luciferase assay and RNA immunoprecipitation (RIP) assay. Finally, the effect of 150Rik on cell proliferation through the miR-451/insulin-like growth factor 1 receptor (IGF1R)/mitogen-activated protein kinases (p38MAPK) pathway was detected by EdU, flow cytometry analysis, western blot.ResultsWe found that 150Rik, an evolutionarily conserved lncRNA, was significantly upregulated in renal tissue of db/db DN mice and in mesangial cells (MCs) cultured under a high glucose condition. Further, overexpression or knockdown of 150Rik was found to regulate cell proliferation in MCs. Moreover, 150Rik was found to interact with miR-451 in both a direct and argonaute-2 (Ago2)-dependent manner. Results also revealed that overexpression of 150Rik inhibited cell proliferation through the miR-451/IGF1R/p38MAPK pathway in MCs under the high glucose condition, while knockdown of 150Rik increased cell proliferation via the miR-451/IGF1R/p38MAPK pathway.ConclusionTaken together, these results provide new insight into the association between 150Rik and the miR-451/IGF1R/p38MAPK signaling pathway during DN progression.