M6A methylation-mediated elevation of SM22α inhibits the proliferation and migration of vascular smooth muscle cells and ameliorates intimal hyperplasia in type 2 diabetes mellitus

Abstract Abnormal proliferation of vascular smooth muscle cells (VSMCs) induced by insulin resistance facilitates intimal hyperplasia of type 2 diabetes mellitus (T2DM) and N6-methyladenosine (m 6 A) methylation modification mediates the VSMC proliferation. This study aimed to reveal the m 6 A methylation modification regulatory mechanism. In this study, m 6 A demethylase FTO was elevated in insulin-treated VSMCs and T2DM mice with intimal injury. Functionally, FTO knockdown elevated m 6 A methylation level and further restrained VSMC proliferation and migration induced by insulin. Mechanistically, FTO knockdown elevated Smooth muscle 22 alpha (SM22α) expression and m 6 A-binding protein IGF2BP2 enhanced SM22α mRNA stability by recognizing and binding to m 6 A methylation modified mRNA. In vivo studies confirmed that the elevated m 6 A modification level of SM22α mRNA mitigated intimal hyperplasia in T2DM mice. Conclusively, m 6 A methylation-mediated elevation of SM22α restrained VSMC proliferation and migration and ameliorated intimal hyperplasia in T2DM.