MeCP2 promotes keloid progression by regulating ADAM12 expression and Wnt/β-catenin pathway

Abstract

Background: Methyl-CpG binding protein 2 (MeCP2) has been reported to participate in the progression of human diseases. In this study, we aimed to explore the functions and related mechanisms of MeCP2 in keloid progression. Methods: Expression of MeCP2 and A Disintegrin and Metalloprotease 12 (ADAM12) was measured by qRT-PCR and western blot assay. Cell proliferation was explored by CCK-8 assay. Cell migration and invasion were investigated by transwell assay. Cell apoptosis was analyzed by flow cytometry analysis. The relation between ADAM12 and MeCP2 was analyzed by CHIP RT-PCR assay and dual-luciferase reporter assay. Results: ADAM12 was highly expressed in keloid tissues and keloid fibroblasts. Silencing of ADAM12 suppressed the proliferation, migration, invasion, ECM accumulation, facilitated the apoptosis and blocked Wnt/β-catenin pathway in keloid fibroblasts. Furthermore, we verified that MeCP2 could modulate ADAM12 expression by binding to its promoter. MeCP2 knockdown inhibited keloid fibroblasts proliferation, migration, invasion and ECM accumulation, with ADAM12 overexpression ameliorated the effects. Besides, MeCP2 silencing inhibited Wnt/β-catenin pathway by altering ADAM12 expression. Conclusion: MeCP2 regulated ADAM12 expression and Wnt/β-catenin pathway to promote cell proliferation, migration, invasion and ECM accumulation in keloid fibroblasts.