Inhibition of microRNA-214 promotes epithelial-mesenchymal transition process and induces interstitial cystitis in postmenopausal women by upregulating Mfn2.
Inhibition of microRNA-214 promotes epithelial-mesenchymal transition process and induces interstitial cystitis in postmenopausal women by upregulating Mfn2.
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microRNA-214的抑制可促进上皮 - 间质转变过程，并通过上调MFN2诱导绝经后妇女的间质膀胱炎。
DOI：
10.1038/emm.2017.98
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发表时间：
2017-07-21
影响因子：
12.8
通讯作者：
Xue W
中科院分区：
文献类型：
--
作者：
Lv JW;Wen W;Jiang C;Fu QB;Gu YJ;Lv TT;Li ZD;Xue W
我们的研究旨在通过靶向Mitofusin 2 （Mfn2）探讨microRNA-214 （miR-214）在绝经后妇女上皮间充质转化（EMT）过程和间质性膀胱炎（IC）发展中的作用。收集绝经后妇女的IC膀胱组织和邻近的正常膀胱组织。免疫组化（IHC）染色。通过双荧光素酶报告基因检测确定miR-214和Mfn2之间的靶标关系。从绝经后大鼠中提取脂肪源性间充质干细胞（ADMSCs），并将其分为空白、模拟物、miR-214抑制剂、模拟阴性对照（NC）、抑制剂NC、Mfn2 siRNA、miR-214抑制剂和Mfn2 siRNA组。将转染的ADMSCs分泌的外泌体注入绝经后大鼠膀胱。采用qRT-PCR和western blotting检测miR-214、Mfn2 mRNA和EMT标志物的表达。证实了Mfn2是miR-214在IC中的靶基因，与正常膀胱组织相比，IC膀胱组织中miR-214水平降低，而Mfn2水平升高。与空白组比较，miR-214模拟物组和Mfn2组的N-cadherin、Fibronectin、Twist1、Snail和Vimentin mRNA和蛋白的表达水平升高，而Mfn2、E-cadherin和ZO-1 mRNA和蛋白的表达水平降低。MiR-214抑制剂组MiR-214的表达以及N-cadherin、Fibronectin、Twist1、Snail和Vimentin mRNA和蛋白的表达水平降低，而Mfn2、E-cadherin和ZO-1 mRNA和蛋白的表达水平升高。我们的研究结果表明，抑制miR-214促进EMT过程，并通过上调Mfn2促进膀胱壁纤维化，从而导致绝经后妇女IC的发生。
Our study aims to investigate the roles that microRNA-214 (miR-214) plays in the epithelial mesenchymal transition (EMT) process and the development of interstitial cystitis (IC) in postmenopausal women by targeting Mitofusin 2 (Mfn2). IC bladder tissues and adjacent normal bladder tissues were collected from postmenopausal women. Immunohistochemistry (IHC) staining was conducted. The target relationship between miR-214 and Mfn2 was determined by a dual luciferase reporter gene assay. Adipose-derived mesenchymal stem cells (ADMSCs) were extracted from postmenopausal rats and assigned to the blank, mimics, miR-214 inhibitors, mimics negative control (NC), inhibitors NC, Mfn2 siRNA, miR-214 inhibitors and Mfn2 siRNA groups. Exosomes secreted by transfected ADMSCs were instilled into the bladders of postmenopausal rats. The expression of miR-214 and Mfn2 mRNA and EMT markers was assessed by qRT-PCR and western blotting. It was confirmed that Mfn2 was the target gene of miR-214 in IC. Compared with the normal bladder tissues, miR-214 decreased, but Mfn2 increased in IC bladder tissues. Compared with the blank group, the expression of miR-214 and the expression levels of N-cadherin, Fibronectin, Twist1, Snail and Vimentin mRNA and protein increased, whereas the expression levels of Mfn2, E-cadherin and ZO-1 mRNA and protein decreased in the miR-214 mimics and Mfn2 groups. The expression of MiR-214 and the expression levels of N-cadherin, Fibronectin, Twist1, Snail and Vimentin mRNA and protein decreased, whereas the expression levels of Mfn2, E-cadherin and ZO-1 mRNA and protein increased in the miR-214 inhibitors group. Our findings indicate that the inhibition of miR-214 promotes the EMT process and contributes to bladder wall fibrosis by up-regulating Mfn2, thus leading to the occurrence of IC in postmenopausal women.
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