KLF4公司
表型转换
表型
糖酵解
细胞生物学
下调和上调
血管平滑肌
生物
遗传学
生物化学
诱导多能干细胞
新陈代谢
内分泌学
基因
胚胎干细胞
平滑肌
作者
Xinhua Zhang,Bin Zheng,Lingdan Zhao,Jian Shen,Zhan Yang,Yu Zhang,Ruirui Fan,Manli Zhang,Dong Ma,Lemin Zheng,Mingming Zhao,Huirong Liu,Jin‐Kun Wen
标识
DOI:10.1038/s42003-022-04302-y
摘要
Vascular smooth muscle cells (VSMCs) within atherosclerotic lesions undergo a phenotypic switching in a KLF4-dependent manner. Glycolysis plays important roles in transdifferentiation of somatic cells, however, it is unclear whether and how KLF4 mediates the link between glycolytic switch and VSMCs phenotypic transitions. Here, we show that KLF4 upregulation accompanies VSMCs phenotypic switching in atherosclerotic lesions. KLF4 enhances the metabolic switch to glycolysis through increasing PFKFB3 expression. Inhibiting glycolysis suppresses KLF4-induced VSMCs phenotypic switching, demonstrating that glycolytic shift is required for VSMCs phenotypic switching. Mechanistically, KLF4 upregulates expression of circCTDP1 and eEF1A2, both of which cooperatively promote PFKFB3 expression. TMAO induces glycolytic shift and VSMCs phenotypic switching by upregulating KLF4. Our study indicates that KLF4 mediates the link between glycolytic switch and VSMCs phenotypic transitions, suggesting that a previously unrecognized KLF4-eEF1A2/circCTDP1-PFKFB3 axis plays crucial roles in VSMCs phenotypic switching.
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