PKM2通过调节糖酵解，线粒体裂变和融合来调节VR-EPC的血管生成。,Journal of Cellular Physiology

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PKM2通过调节糖酵解，线粒体裂变和融合来调节VR-EPC的血管生成。
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-02-03 , DOI: 10.1002/jcp.29549
Ranyue Ren ₁ , Jiachao Guo ₁ , Jia Shi ₁ , Yong Tian ₁ , Mengwei Li ₁ , Hao Kang ₁

Affiliation

血管驻留内皮祖细胞（VR-EPC）具有一定的分化为内皮细胞（EC）并参与血管生成过程的能力。糖酵解和线粒体的分裂与融合在血管生成中起关键作用。丙酮酸激酶肌肉同工酶2（PKM2）介导能量代谢和线粒体形态，在我们的研究中被视为VR-EPCs血管生成的焦点。从12周龄的Sprague-Dawley大鼠的心脏中分离出VR-EPC。通过管形成测定，伤口愈合测定，transwell测定和鸡绒膜尿囊膜测定来评估PKM2在血管生成中的作用。Western印迹分析，流式细胞仪，线粒体膜电位检测，活性氧（ROS）检测，免疫荧光染色，和实时定量聚合酶链反应用于研究PKM2调节VR-EPCs血管生成的潜在机制。我们探讨了PKM2在VR-EPCs血管生成中的功能。DASA-58（PKM2的激活剂）促进了VR-EPC的增殖和PKM2的活性，还可以促进血管生成的分化。同时，DASA-58显着增强了糖酵解，线粒体融合，线粒体膜电位略有增加，并使ROS保持在较低水平。C3k是PKM2的抑制剂，可抑制PKM2活性，血管生成相关基因的表达和管形成。此外，C3k大大降低了糖酵解和线粒体膜电位，同时显着促进了线粒体裂变和ROS水平。PKM2的激活可以通过调节糖酵解，线粒体裂变和融合来促进VR-EPC的血管生成。相反，PKM2抑制剂具有相反的作用。

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PKM2 regulates angiogenesis of VR-EPCs through modulating glycolysis, mitochondrial fission, and fusion.

Vascular resident endothelial progenitor cells (VR‐EPCs) have a certain ability to differentiate into endothelial cells (ECs) and participate in the process of angiogenesis. Glycolysis and mitochondrial fission and fusion play a pivotal role in angiogenesis. Pyruvate kinase muscle isoenzyme 2 (PKM2), which mediates energy metabolism and mitochondrial morphology, is regarded as the focus of VR‐EPCs angiogenesis in our study. VR‐EPCs were isolated from the hearts of 12‐weeks‐old Sprague‐Dawley rats. The role of PKM2 on angiogenesis was evaluated by tube formation assay, wound healing assay, transwell assay, and chick chorioallantoic membrane assay. Western blot analysis, flow cytometry, mitochondrial membrane potential detection, reactive oxygen species (ROS) detection, immunofluorescence staining, and quantitative real‐time polymerase chain reaction were used to investigate the potential mechanism of PKM2 for regulating VR‐EPCs angiogenesis. We explored the function of PKM2 on the angiogenesis of VR‐EPCs. DASA‐58 (the activator of PKM2) promoted VR‐EPCs proliferation and PKM2 activity, it also could promote angiogenic differentiation. At the same time, DASA‐58 significantly enhanced glycolysis, mitochondrial fusion, slightly increased mitochondrial membrane potential, and maintained ROS at a low level. C3k, an inhibitor of PKM2, inhibited PKM2 activity, expression of angiogenesis‐related genes and tube formation. Besides, C3k drastically reduced glycolysis and mitochondrial membrane potential while significantly promoting mitochondrial fission and ROS level. Activation of PKM2 could promote VR‐EPCs angiogenesis through modulating glycolysis, mitochondrial fission and fusion. By contrast, PKM2 inhibitor has opposite effects.

更新日期：2020-02-03

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