VEGF promotes endothelial progenitor cell differentiation and vascular repair through connexin 43

Stem Cell Research & Therapy

Shangcheng Xu¹  Chunxin Xu²  Xiaohui Zhao²  Huanyun Liu²  Lufeng Li²  Mengyang Deng²  Xuejun Yu²  Mingbao Song² 

[1] Department of Occupational Health, Third Military Medical University;Institute of Cardiovascular Research, Xinqiao Hospital, Third Military Medical University;

关键词: Endothelial progenitor cell;    Vascular endothelial growth factor;    Connexin 43;    Differentiation;    Vascular repair;   

DOI  :  10.1186/s13287-017-0684-1

来源: DOAJ

【 摘 要 】

Abstract Background Endothelial progenitor cell (EPC) differentiation is considered crucial for vascular repair. Vascular endothelial growth factor (VEGF) induces EPC differentiation, but the underlying mechanism of this phenomenon remains unclear. Connexin 43 (Cx43) is reported to be involved in the regulation of stem cell differentiation. Therefore, we sought to determine whether Cx43 is involved in VEGF-induced EPC differentiation and vascular repair. Methods Rat spleen-derived EPCs were cultured and treated with various concentrations of VEGF (0, 10, or 50 ng/mL), and the relationship between EPC differentiation and Cx43 expression was evaluated. Thereafter, fluorescence redistribution after photobleaching was performed to assess the relationship between adjacent EPC differentiation and Cx43-induced gap junction intercellular communication (GJIC). After carotid artery injury, EPCs pretreated with VEGF were injected into the tail veins, and the effects of Cx43 on vascular repair were evaluated. Results EPCs cultured with VEGF exhibited accelerated differentiation and increased expression of Cx43. However, inhibition of Cx43 expression using short interfering RNA (siRNA) attenuated EPC GJIC and consequent EPC differentiation. VEGF-pretreated EPC transplantation promoted EPC homing and reendothelialization, and inhibited neointimal formation. These effects were attenuated by siRNA inhibition of Cx43. Conclusions Our results from in vivo and in vitro experiments indicated that VEGF promotes EPC differentiation and vascular repair through Cx43.

【 授权许可】

Unknown