基因敲除
血管平滑肌
内膜增生
化学
甲基化
2型糖尿病
内分泌学
生物
内科学
糖尿病
增生
医学
DNA甲基化
细胞凋亡
基因表达
平滑肌
生物化学
基因
作者
Baofu Zhang,Ziheng Wu,Jie Deng,Haojie Jin,Weibiao Chen,Sai Zhang,Xiujie Liu,Wan-Tie Wang,Xiangtao Zheng
标识
DOI:10.1515/hsz-2021-0296
摘要
Abnormal proliferation of vascular smooth muscle cells (VSMCs) induced by insulin resistance facilitates intimal hyperplasia of type 2 diabetes mellitus (T2DM) and N6-methyladenosine (m6A) methylation modification mediates the VSMC proliferation. This study aimed to reveal the m6A methylation modification regulatory mechanism. In this study, m6A demethylase FTO was elevated in insulin-treated VSMCs and T2DM mice with intimal injury. Functionally, FTO knockdown elevated m6A methylation level and further restrained VSMC proliferation and migration induced by insulin. Mechanistically, FTO knockdown elevated Smooth muscle 22 alpha (SM22α) expression and m6A-binding protein IGF2BP2 enhanced SM22α mRNA stability by recognizing and binding to m6A methylation modified mRNA. In vivo studies confirmed that the elevated m6A modification level of SM22α mRNA mitigated intimal hyperplasia in T2DM mice. Conclusively, m6A methylation-mediated elevation of SM22α restrained VSMC proliferation and migration and ameliorated intimal hyperplasia in T2DM.
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