[1]姜文豪,易红,彭睿,等.长链非编码RNA Gm4419通过NF-κB信号通路调控高糖下系膜细胞炎症因子的表达[J].第三军医大学学报,2018,40(07):577-583.
 JIANG Wenhao,YI Hong,PENG Rui,et al.LncRNA Gm4419 regulates inflammatory cytokines expression via NF-κB signaling pathway in mesangial cells under high glucose condition[J].J Third Mil Med Univ,2018,40(07):577-583.
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长链非编码RNA Gm4419通过NF-κB信号通路调控高糖下系膜细胞炎症因子的表达(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
40卷
期数:
2018年第07期
页码:
577-583
栏目:
基础医学
出版日期:
2018-04-15

文章信息/Info

Title:
LncRNA Gm4419 regulates inflammatory cytokines expression via NF-κB signaling pathway in mesangial cells under high glucose condition
作者:
姜文豪易红彭睿彭惠民张政
重庆医科大学基础医学院:细胞生物学及遗传学教研室,生物信息学教研室,实验教学中心
Author(s):
JIANG Wenhao YI Hong PENG Rui PENG Huimin ZHANG Zheng

Department of Cell Biology and Medical Genetics, Department of Bioinformatics, Experimental Teaching Center, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, China

关键词:
LncRNAGm4419NF-&kappaB肾小球系膜细胞炎症
Keywords:
lncRNA Gm4419 NF-&kappaB glomerular mesangial cells inflammation
分类号:
R322.61;R329.28;R394.2
文献标志码:
A
摘要:

目的     探讨长链非编码RNA Gm4419通过核转录因子-kappa B (nuclear factor-kappa B, NF-κB)信号通路对高糖培养的肾小球系膜细胞炎症因子表达的影响。方     法在高、低糖培养的小鼠肾小球系膜细胞中,采用RT-qPCR检测Gm4419的亚细胞分布及NF-κB亚基p50和p65 的表达水平;采用RT-qPCR及免疫荧光检测上、下调Gm4419后炎症相关因子TNF-α和MCP-1的表达;采用生物信息技术分析Gm4419与p50和p65关系;采用Western blot检测上、下调Gm4419后细胞核中p50和p65的表达水平,以及检测特异性p50抑制剂对过表达Gm4419影响MCP-1表达的作用。结果     Gm4419在肾小球系膜细胞高糖组表达水平显著高于低糖组(P<0.05),且主要分布在系膜细胞的细胞质中。同时,在低糖组过表达Gm4419后MCP-1、TNF-α表达水平显著增加(P<0.01);而在高糖组沉默Gm4419后MCP-1、TNF-α表达水平显著减少(P<0.01)。此外,Gm4419与NF-κB亚基p50和p65均存在潜在结合位点,过表达Gm4419后胞核p50和p65蛋白表达水平显著增加,NF-κB活化增强(P<0.01);而沉默Gm4419后胞核p50和p65蛋白表达水平显著降低,NF-κB活化减弱(P<0.01),且过表达Gm4419增加MCP-1表达的效应可被特异性p50抑制剂阻断。结论    Gm4419可能在促进高糖下系膜细胞炎症因子表达中扮演重要角色,其机制可能涉及NF-κB信号通路。

Abstract:

Objective     To investigate the mechanism of long non-coding RNA (lncRNA) Gm4419 regulating the expression of inflammatory cytokines in glomerular mesangial cells under high glucose condition via mediating nuclear factor-kappa B (NF-κB) signaling pathway. Methods     The subcellular distribution of Gm4419 and expression of NF-κB subunits p50 and p65 were detected by RT-qPCR in mouse glomerular mesangial cells (MCs) under high or low glucose condition. Moreover, RT-qPCR and immunofluorescence assay were used to measure the expression of MCP-1 and TNF-α when Gm4419 was up- or down regulated. Additionally, bioinformatics analysis was carried out to predict the relationship between Gm4419 and NF-κB. Western blot assay was used to determine the expression of p50 and p65 in the nucleus of MCs, and the effect of specific p50 inhibitor on the expression of MCP-1 was studied in MCs with Gm4419 overexpression. Results     The expression of Gm4419 was significantly higher in MCs under high glucose condition than those under low condition (P<0.05), and Gm4419 mainly located in the cytoplasm. The expression levels of MCP-1 and TNF-α were significantly increased in the low glucose group when Gm4419 was overexpressed (P<0.01), while the levels were decreased in high glucose group when Gm4419 was silenced (P<0.01). Moreover, the binding sites of Gm4419 and p50 and p65 were predicted, and overexpression of Gm4419 resulted in the increases in p50 and p65 expression levels and enhancement in NF-κB activity (P<0.01). However, silencing Gm4419 induced opposite effects (P<0.01). Additionally, specific p50 inhibitor could block the up-reguation of MCP-1 induced by Gm4419 over-expression. Conclusion     Gm4419 may play an important role in the enhanced expression of inflammatory cytokines in mesangial cells under high glucose condition, and its mechanism may be related to the NF-κB signaling pathway.
 

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相似文献/References:

[1]易红,彭睿,孙艳,等.lncRNA-Gm4419对高糖培养的肾小球系膜细胞增殖和纤维化的影响[J].第三军医大学学报,2017,39(03):216.
 Yi Hong,Peng Rui,Sun Yan,et al.Effect of lncRNA-Gm4419 on proliferation and fibrosis in high glucose-induced glomerulus mesangial cells[J].J Third Mil Med Univ,2017,39(07):216.

更新日期/Last Update: 2018-04-09