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

Ranyue Ren; Jiachao Guo; Jia Shi; Yong Tian; Mengwei Li; Hao Kang

doi:10.1002/jcp.29549

journal article Feb 03, 2020

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

Ranyue Ren Jiachao Guo Jia Shi

Yong Tian

Mengwei Li

Hao Kang

Journal of Cellular Physiology Vol. 235 No. 9 pp. 6204-6217 · Wiley

View at Publisher Save 10.1002/jcp.29549

Abstract

AbstractVascular 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.

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Details

Published: Feb 03, 2020
Vol/Issue: 235(9)
Pages: 6204-6217
License: View

Authors

R

Ranyue Ren