Microrna-139-5p inhibits epithelial-mesenchymal transition and fibrosis in post-menopausal women with interstitial cystitis by targeting LPAR4 via the PI3K/Akt signaling pathway

作者：Jiang, Chen; Tong, Zhen; Fang, Wei-Lin; Fu, Qi-Bo; Gu, Yin-Jun; Lv, Ting-Ting; Liu, Dong-Ming; Xue, Wei; Lv, Jian-Wei^*

来源：Journal of Cellular Biochemistry, 2018, 119(8): 6429-6441.

DOI：10.1002/jcb.26610

• epithelial-mesenchymal transition
• fibrosis
• interstitial cystitis
• LPAR4
• microrna-139-5P
• PI3K
• AKT signaling pathway

The study explores whether miR-139-5p targeting LPAR4 affects epithelial-mesenchymal transition (EMT) and fibrosis in post-menopausal women with interstitial cystitis (IC) via the PI3K/Akt signaling pathway. Bladder tissues of IC and normal bladder tissues were collected. The pathology of bladder tissues was observed by HE, Masson and Picrosirius red staining. LPAR4 positive expression rate were determined by IHC. ELISA was performed to detect the levels of IL-6, IL-8, IL-10, and TNF-. Rat IC models were randomized into seven different groups. miR-139-5p, LPAR1, LPAR2, LPAR3, LPAR4, LPAR5, P13K, Akt, E-cadherin, N-cadherin, Vimentin, TGF-1, and CTGF expression were determined by RT-qPCR and Western blotting. Dual luciferase reporter gene assay verified that LPAR4 is a target gene of miR-139-5p. Fibrosis was a pathological manifestation of IC. The IC group showed higher LPAR4, PI3K, Akt, p-PI3K, p-Akt, N-cadherin, Vimentin, TGF-1, and CTGF expression but lower miR-139-5p and E-cadherin expression than the normal group. The levels of IL-6, IL-8, IL-10, and TNF- expression decreased while HB-EGF increased in the IC group in comparison of the normal group. Compared with the blank and NC groups, E-cadherin expression was increased in the miR-139-5p mimic and siRNA-LPAR4 groups, while LPAR4, PI3K, Akt, p-P13K, p-Akt, N-cadherin, Vimentin, TGF-1, and CTGF expression were decreased. An opposite trend was found in the miR-139-5p inhibitor group. The miR-139-5p decreased in the miR-139-5p inhibitor+siRNA-LPAR4 and miR-139-5p inhibitor+wortmannin groups. Conclusively, miR-139-5p targeting LPAR4 inhibits EMT and fibrosis in post-menopausal IC women through the PI3K/Akt signaling pathway.

• 出版日期2018-8
• 单位上海交通大学