Effect of metformin on TGF-β1-induced fibrosis in human endometrial stromal cells / 解放军医学杂志

ABSTRACT

[Abstract] Objective To explore the effect of metformin on the fibrosis of human endometrial stromal cells (HESCs) induced by transforming growth factor-β1 (TGF-β1). Methods The in vitro model of endometrial fibrosis was established using TGF-β1 treated HESCs, and then treated with TGF-β1 in presence or absence of metformin at different concentrations (10, 50, 200 μmol/L). There set 5 experimental groups normal control group, model group, 10 μmol/L metformin intervention group, 50 μmol/L metformin intervention group, and 200 μmol/L metformin intervention group. The mRNA and protein expression levels of α-smooth muscle actin (α-SMA), collagen type 1 alpha 1 (Col1α1) and fibronectin were detected by qPCR and Western blotting. The cell proliferation was detected by CCK-8 and EdU staining. Results The mRNA expression levels of α-SMA in the 5 groups were 1.003±0.108, 4.329±0.342, 3.383±0.342, 2.310±0.263 and 1.566±0.205; of Col1α1 were 1.002±0.299, 3.462±0.695, 2.342±0.531, 1.970±0.336 and 1.450±0.233; and of fibronectin were 1.000±0.225, 4.455±0.524, 3.164±0.317, 2.728±0.311 and 2.145±0.218; the differences between groups were statistically significant (P0.05). The OD values of the 5 groups were 0.313±0.091, 1.497±0.081, 1.095±0.059, 0.895±0.046 and 0.560±0.082, and the positive rate of EdU cells were 12.665±3.146, 47.650±4.656, 37.568±2.549, 32.050±3.652 and 26.050±3.453, showing statistically significant differences between the groups (P<0.001). Compared with normal control group, the proliferation capacity of model group increased significantly (P<0.01). Compared with model group, the proliferation capacity of 10, 50 and 200 μmol/L metformin intervention group reduced significantly in a dose-dependent manner (P<0.01). Conclusion Metformin may play an anti-fibrosis effect via inhibiting TGF-β1-induced myofibroblast differentiation as well as ECM synthesis and proliferation in HESCs.