Putrescine promotes MMP9-induced angiogenesis in skeletal muscle through hydrogen peroxide/METTL3 pathway

文献类型： 外文期刊

第一作者： Hu, Chengjun

作者： Hu, Chengjun;Ji, Fengjie;Lv, Renlong;Zhou, Hanlin;Hou, Guanyu;Xu, Tieshan;Hu, Chengjun;Zhou, Hanlin;Hou, Guanyu;Xu, Tieshan

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关键词： Hydrogen peroxide; MMP9; METTL3; Putrescine; Skeletal muscle angiogenesis

期刊名称：FREE RADICAL BIOLOGY AND MEDICINE （ 影响因子：7.4； 五年影响因子：7.9 ）

ISSN： 0891-5849

年卷期： 2024 年 212 卷

页码：

收录情况： SCI

摘要： Blood vessels play a crucial role in the development of skeletal muscle, ensuring the supply of nutrients and oxygen. Putrescine, an essential polyamine for eukaryotic cells, has an unclear impact on skeletal muscle angiogenesis. In this study, we observed lower vessel density and reduced putrescine level in the muscle of lowbirth-weight piglet models, and identified a positive correlation between putrescine content and muscle vessel density. Furthermore, putrescine was found to promote angiogenesis in skeletal muscle both in vitro and in vivo by targeting matrix metalloproteinase 9 (MMP9). On a mechanistic level, putrescine augmented the expression of methyltransferase like 3 (METTL3) by attenuating hydrogen peroxide production, thereby increasing the level of N6-methyladenosine (m6A)-modified MMP9 mRNA. This m6A-modified MMP9 mRNA was subsequently recognized and bound by the YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), enhancing the stability of MMP9 mRNA and its protein expression, consequently accelerating angiogenesis in skeletal muscle. In summary, our findings suggest that putrescine enhances MMP9-mediated angiogenesis in skeletal muscle via the hydrogen peroxide/METTL3 pathway

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