Inhibition of microRNA-214 promotes epithelial–mesenchymal transition process and induces interstitial cystitis in postmenopausal women by upregulating Mfn2.
- Author:
Jian Wei LV
1
;
Wei WEN
;
Chen JIANG
;
Qi Bo FU
;
Yin Jun GU
;
Ting Ting LV
;
Zhen Dong LI
;
Wei XUE
Author Information
- Publication Type:Original Article
- MeSH: Animals; Blotting, Western; Cadherins; Cystitis, Interstitial*; Epithelial-Mesenchymal Transition; Exosomes; Female; Fibronectins; Fibrosis; Genes, Reporter; Humans; Immunohistochemistry; Luciferases; Mesenchymal Stromal Cells; Rats; RNA, Messenger; RNA, Small Interfering; Snails; Urinary Bladder; Vimentin
- From:Experimental & Molecular Medicine 2017;49(7):e357-
- CountryRepublic of Korea
- Language:English
- Abstract: 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.
