MicroRNA-29 mediates TGFβ1-induced extracellular matrix synthesis by targeting wnt/β-catenin pathway in human orbital fibroblasts

作者：Tan, Jia; Tong, Bo-Ding; Wu, Yu-Jie; Xiong, Wei^*

来源：International Journal of Clinical and Experimental Pathology, 2014, 7(11): 7571-7577.

• Orbital fibrosis
• TGF beta 1
• miR-29
• wnt/beta-catenin pathway

Purpose: Transforming growth factor 1 (TGF beta 1) is very important in the synthesis and degradation of extracellular matrix (ECM) and also in the mediation of human orbital fibroblasts (OFs) proliferation. MicroRNA-29 (MiR-29) plays an important role in this process. In the present study, the effects of TGF beta 1 on the expression of miR-29 and whether miR-29 is involved in pro-survival signaling pathways mediated by TGF beta 1 were examined in human OFs. Methods: Detecting the influence of TGF beta 1 on the expression of miR-29a/b/c by real-time PCR analysis. Using 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) to detecting the influence of miR-29 on the increased proliferation caused by TGF-beta 1 on the human orbital fibroblasts. Using soft agar assay to detecting the influence of miR-29 on the increased colony formation caused by TGF-beta 1 on the human orbital fibroblasts. Western blot was used to detect the specific mechanisin. Results: TGF beta 1 treatment decreases the expression of miR-29 in OFs. In the cultured OFs, the value of optical density (OD) in the group treated with miR-29 is lower than that in the group treated without miR-29 (P < 0.05). In the cultured OFs, the ratio of colony formation in the group treated with miR-29 is lower than that in the group treated without miR-29 (P < 0.05). In OFs, miR-29 decreases the secretion of Wnt3a and activation of beta-catenin whether the treatment of TGF beta 1 was used or not. MiR-29 decreases expression of Collagen, type I, alpha 1 (COL1A1) through down-regulation of wnt/beta-catenin pathway. Conclusions: In OFs TGF beta 1 treatment decreases expression of miR-29 which can cause the inhibition of normal ability of TGF beta 1. MiR-29 inhibits TGF beta 1-induced proliferation of OFS cell and decreases colony formation of OFS cell after TGF beta 1 treatment. MiR-29 Mediates TGF beta 1-induced Extracellular matrix synthesis through activation of Wnt/beta-catenin pathway in human OFs.

• 出版日期2014
• 单位中南大学