KLF4-PFKFB3-driven glycolysis is essential for phenotypic switching of vascular smooth muscle cells.
KLF4-PFKFB3-driven glycolysis is essential for phenotypic switching of vascular smooth muscle cells.
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KLF4-PFKFB3驱动的糖酵解对于血管平滑肌细胞的表型转换至关重要
DOI：
10.1038/s42003-022-04302-y
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发表时间：
2022-12-05
影响因子：
5.9
通讯作者：
中科院分区：
文献类型：
--
作者：
动脉粥样硬化病变内的血管平滑肌细胞（VSMCs）以klf4依赖的方式进行表型转换。糖酵解在体细胞转分化中发挥着重要作用，然而，KLF4是否以及如何介导糖酵解开关与VSMCs表型转变之间的联系尚不清楚。本研究表明，在动脉粥样硬化病变中，KLF4上调伴随着VSMCs表型转换。KLF4通过增加PFKFB3的表达来促进糖酵解的代谢转换。抑制糖酵解抑制klf4诱导的VSMCs表型转换，表明糖酵解转移是VSMCs表型转换所必需的。在机制上，KLF4上调circCTDP1和eEF1A2的表达，两者协同促进PFKFB3的表达。TMAO通过上调KLF4诱导糖酵解移位和VSMCs表型转换。我们的研究表明，KLF4介导糖酵解开关与VSMCs表型转变之间的联系，表明先前未被识别的KLF4- eef1a2 /circCTDP1-PFKFB3轴在VSMCs表型转换中起着至关重要的作用。klf4诱导的血管平滑肌细胞表型转换发生在动脉粥样硬化中。现在，KLF4被证明通过环状RNA CTDP1和真核延伸因子eEF1A2诱导糖酵解转移，包括上调PFKFB3的表达。
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. KLF4-induced phenotypic switching of vascular smooth muscle cells occurs in atherosclerosis. Now, KLF4 is shown to induce a glycolytic shift involving upregulation of PFKFB3 expression through circular RNA CTDP1 and eukaryotic elongation factor eEF1A2.
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