Metformin alleviates the progression of oral submucous fibrosis through downregulation of metastasis associated lung adenocarcinoma transcript 1 (MALAT1).

BACKGROUND: /purpose: Emerging evidence demonstrates the anti-fibrotic properties of metformin, a first-line anti-diabetic drug; however, its inhibitory effects on oral fibrogenesis warrant further evaluation.

MATERIALS AND METHODS: The cytotoxic effects of metformin on normal and fibrotic buccal mucosal fibroblasts (fBMFs) derived from OSF tissues were evaluated using the MTT assay. Collagen gel contraction, wound healing, and transwell migration assays were carried out to assess myofibroblast features. In addition, the expression levels of alpha-1 type I collagen (COL1A1), alpha-smooth muscle actin (α-SMA) and Smad2 were measured. Moreover, RNA sequencing was performed to explore potential targets participating in the anti-fibrotic effects of metformin.

RESULTS: A lower dose of metformin was sufficient to inhibit the proliferation of fBMFs without affecting normal BMFs, and to attenuate various myofibroblast characteristics, including collagen gel contraction, wound healing, transwell migration capacities, and the expression of fibrosis markers. Additionally, we showed that administration of metformin prevented the arecoline-induced myofibroblast activation. Most importantly, our results suggest that metformin may exert suppressive effects on myofibroblast activities by inhibiting ROS accumulation through the downregulation of MALAT1.

CONCLUSION: These findings indicate that metformin may serve as a preventive agent against OSF progression.