干扰素-α1b通过miR141抑制ZEB1/SIP1信号通路改善IgA肾病肾小管上皮细胞上皮-间充质转化和纤维化  

Interferon-α1b ameliorates EMT and fibrosis of renal tubular epithelial cells in IgA nephropathy by miRNA-141 suppressing ZEB1/SIP1 signaling pathway

作　　者：刘红艳[1] 冯琦[1] 胡晓娟 刘颖[1] 徐超 布合力其·麦麦提[1] LIU Hongyan;FENG Qi;HU Xiaojuan;LIU Ying;XU Chao;BUHELIQI Maimaiti(Department of Nephrology,the Fifth Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China)

机构地区：[1]新疆医科大学第五附属医院肾病科,新疆乌鲁木齐830054

出　　处：《现代药物与临床》2024年第12期3014-3020,共7页Drugs & Clinic

基　　金：新疆少数民族科技人才特殊培养计划科研项目(2023D03016)。

摘　　要：目的研究干扰素-α1b通过mi R141抑制锌指E盒结合同源蛋白1(ZEB1)/Smad相互作用蛋白1(SIP1)信号通路改善Ig A肾病肾小管上皮细胞上皮-间充质转化(EMT)和纤维化的影响。方法通过MDCK细胞模型验证干扰素-α1b对mi R-141表达、ZEB1/SIP1信号通路的影响;构建Ig A肾病大鼠模型,按照随机分为对照组、模型组、干扰素-α1b(15、30μg)组、泼尼松组,每组8只,连续治疗8周。监测大鼠肾功能、炎症因子水平、Ig A沉积和肾脏病理变化;分析mi R-141、ZEB1、SIP1、E-钙黏蛋白(E-cadherin)的表达水平。结果体外实验表明,干扰素-α1b能够显著上调MDCK细胞中mi R-141的表达,并降低ZEB1和SIP1蛋白相对表达量(P<0.05)。Ig A肾病大鼠模型中,相比于模型组,干扰素-α1b组大鼠肾功能显著改善,炎症因子肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的分泌水平明显降低,Ig A沉积减少,肾脏损伤得到缓解(P<0.05)。干扰素-α1b能诱导大鼠肾脏中mi R-141显著上调,抑制ZEB1和SIP1蛋白相对表达,上调Ecadherin蛋白相对表达,抑制上皮细胞EMT和纤维化(P<0.05)。结论干扰素-α1b通过上调肾脏中mi R-141的表达,抑制转录因子ZEB1和SIP1表达,减少对E-cadherin的抑制,最终抑制肾小管上皮细胞EMT和纤维化,有效改善Ig A肾病。Objective To investigate the effect of interferon-α1b on improving EMT and fibrosis of renal tubular epithelial cells in IgA nephropathy by inhibiting ZEB1/SIP1 signaling pathway through miR141.Methods MDCK cell model was used to verify the effects of interferon-α1b on miR-141 expression and ZEB1/SIP1 signaling pathway.Rats model of IgA nephropathy was established,and randomly divided into control group,model group,interferon-α1b(15,30μg)group,and prednisone group,with 8 rats in each group,for continuous treatment for 8 weeks.Renal function,levels of inflammatory factors,IgA deposition and renal pathological changes were monitored.The expression levels of miR-141,ZEB1,SIP1 and E-cadherin were analyzed.Results In vitro experiments showed that interferon-α1b could significantly up-regulate the expression of miR-141 in MDCK cells,and reduce the relative expression levels of ZEB1 and SIP1 proteins(P<0.05).In the rat model of IgA nephropathy,compared the model group,the renal function of the rats in the interferon-α1b group was significantly improved,the secretion levels of inflammatory TNF-αand IL-6 were significantly decreased,the deposition of IgA was reduced,and the kidney injury was alleviated(P<0.05).Interferon-α1b can induce significantly up-regulated miR-141 in rat kidney,inhibit the relative expression of ZEB1 and SIP1 proteins,up-regulate the relative expression of E-cadherin protein,and inhibit EMT and fibrosis in epithelial cells(P<0.05).Conclusion Interferon-α1b effectively improves IgA nephropathy by upregulating the expression of miR-141 in the kidney,inhibiting the expression of transcription factors ZEB1 and SIP1,reducing the inhibition of E-cadherin,and ultimately inhibiting renal tubular epithelial cell EMT and fibrosis.

关 键 词：干扰素-Α1B IGA肾病 miR141 锌指E盒结合同源蛋白1 Smad相互作用蛋白1 上皮细胞上皮-间充质转化 肿瘤坏死因子-α 白细胞介素-6 

分 类 号：R965[医药卫生—药理学]