lncRNA ITSN1-2靶向miR-140-3p对高糖诱导的肾小管上皮细胞炎症因子表达和细胞凋亡的影响  

Effect of lncRNA ITSN1⁃2 targeting miR⁃140⁃3p on high glucose⁃triggered renal tubular epithelial cell in⁃flammation and apoptosis

作　　者：周密 李伟[1] 高明松[1] ZHOU Mi;LI Wei;GAO Ming-song(Department of Endocrinology,First Hospital of Wuhan,Hubei Province 430030,China)

机构地区：[1]武汉市第一医院内分泌科,湖北武汉430030

出　　处：《解剖学研究》2025年第1期32-36,42,共6页Anatomy Research

基　　金：武汉市医学科研项目(WZ20A04)。

摘　　要：目的探讨lncRNA ITSN1-2在高糖诱导的肾小管上皮细胞损伤的作用及分子机制。方法将肾小管上皮细胞HK-2随机分为正常对照组(Con)、高糖组(HG)、HG+si-ITSN1-2组、HG+si-NC组、HG+miR-140-3p组、HG+miR-NC组、HG+si-ITSN1-2+anti-miR-140-3p组、HG+si-ITSN1-2+anti-miR-NC组。ITSN1-2和miR-140-3p表达被RT-qPCR分析;酶联免疫吸附试验(ELISA)检测IL-6、TNF-α水平;流式细胞术和蛋白质印迹法分别检测细胞凋亡和蛋白表达;双荧光素酶报告实验验证了ITSN1-2靶向miR-140-3p。结果高糖处理后,ITSN1-2表达,IL-6和TNF-α水平、细胞凋亡率和Bax表达在肾小管上皮细胞HK-2中上调,而miR-140-3p和Bcl-2水平减少(P<0.05);下调lncRNA ITSN1-2或过表达miR-140-3p后,肾小管上皮细胞中IL-6,TNF-α,凋亡率和Bax表达显著减少,而Bcl-2表达提高(P<0.05);lncRNA ITSN1-2靶向负调控miR-140-3p的表达。敲低lncRNA ITSN1-2抑制了高糖引发的HK-2细胞炎症因子表达和细胞凋亡,而下调miR-140-3p缓解了这些影响。结论干扰lncRNA ITSN1-2可能抑制高糖诱导的肾小管上皮细胞炎症因子分泌和细胞凋亡部分通过靶向上调miR-140-3p。Objective To explore the effect and molecular mechanism of lncRNA ITSN1⁃2 on high glucose(HG)⁃induced inflammation and apoptosis.Methods The renal tubular epithelial cells HK⁃2 were divided into nor⁃mal control group(Con),high glucose group(HG),HG+si⁃ITSN1⁃2 group,HG+si⁃NC group,HG+miR⁃140⁃3p group,HG+miR⁃NC group,HG+si⁃ITSN1⁃2+anti⁃miR⁃140⁃3p group,HG+si⁃ITSN1⁃2+anti⁃miR⁃NC group,real⁃time fluorescent quantitative PCR(RT⁃qPCR)to detect ITSN1⁃2 and miR⁃140⁃3p expression levels;enzyme⁃linked immunosorbent assay(ELISA)to detect IL⁃6 and TNF⁃αlevels;flow cytometry to detect cell apoptosis;Western blotting to detect protein expression;Interaction between ITSN1⁃2 and miR⁃140⁃3p was verified using dual⁃luciferase report experiment.Results In renal tubular epithelial cells HK⁃2 induced by HG,ITSN1⁃2 the expression level was enhanced,miR⁃140⁃3p content was reduced,the levels of IL⁃6 and TNF⁃αwere increased,the rate of apoptosis and the expression level of Bax were increased,the expression level of Bcl⁃2 was decreased(P<0.05).After interfer⁃ence with lncRNA ITSN1⁃2 expression or overexpression of miR⁃140⁃3p,IL⁃6 and TNF⁃αlevels were decreased,re⁃nal tubular epithelial cell apoptosis rate and Bax expression level were decreased,and Bcl⁃2 expression level was in⁃creased(P<0.05).lncRNA ITSN1⁃2 targets and negatively regulates the expression of miR⁃140⁃3p.Down⁃regulating of miR⁃140⁃3p reversed the effect of interfering with the expression of lncRNA ITSN1⁃2 on HG⁃triggered HK⁃2 cell inflammation and apoptosis.Conclusion Interfering with the expression of lncRNA ITSN1⁃2 may inhibit the expres⁃sion of inflammatory factors and apoptosis in HG⁃induced renal tubular epithelial cells by targeting up⁃regulation of miR⁃140⁃3p.

关 键 词：肾小管上皮细胞 lncRNA ITSN1-2 miR-140-3p 炎症因子 凋亡 HK细胞 

分 类 号：R73[医药卫生—肿瘤]