Spatio-temporal model of Meox1 expression control involvement of Sca-1-positive stem cells in neointima formation through the synergistic effect of Rho/CDC42 and SDF-1α/CXCR4

Stem Cell Research & Therapy

Long Chen¹  Shan Li²  Xing-yuan Li³  Yan Wang³  Xin Bao³  Liu-liu Shi³  Lu-yuan Yao³  Magdaleena Naemi Mbadhi³  Yun Liu³  Yan Wu³  Sen Zhao³  Ruo-nan Zhang³  Wei Xu³  Jing-xuan Zhang⁴  Zhi-feng Zhang⁴  Yuan-jin Li⁵  Shi-You Chen⁶ 

[1] Cental Lab, Guoyao-Dongfeng Hospital, Hubei University of Medicine, 442000, Shiyan, Hubei, People’s Republic of China;Department of Biochemistry, Faculty of Basic Medical Sciences, Hubei University of Medicine, 442000, Shiyan, Hubei, People’s Republic of China;Department of Physiology, Hubei Key Laboratory of Embryonic Stem Cell Research, Faculty of Basic Medical Sciences, Hubei University of Medicine, 442000, Shiyan, Hubei, People’s Republic of China;Department of Physiology, Hubei Key Laboratory of Embryonic Stem Cell Research, Faculty of Basic Medical Sciences, Hubei University of Medicine, 442000, Shiyan, Hubei, People’s Republic of China;Faculty of Basic Medical Sciences, Institute of Biomedicine, Hubei University of Medicine, 442000, Shiyan, Hubei, People’s Republic of China;Hebei Medical University, 050017, Shijiazhuang, Hebei, People’s Republic of China;The Department of Surgery, University of Missouri, Columbia, USA;

关键词: Meox1;    Sca-1;    Neointima;    SDF-1α;    CDC42;   

DOI  :  10.1186/s13287-021-02466-8

来源: Springer

【 摘 要 】

AimsNeointimal hyperplasia remains a major obstacle in vascular regeneration. Sca-1-positive progenitor cells residing within the vascular adventitia play a crucial role in the assemblage of vascular smooth muscle cell (VSMC) and the formation of the intimal lesion. However, the underlying mechanisms during vascular injury are still unknown.Methods and resultsAneointimal formation rat model was prepared by carotid artery injury using 2F-Forgaty. After vascular injury, Meox1 expressions time-dependently increased during the neointima formation, with its levels concurrently increasing in the adventitia, media, and neointima. Meox1 was highly expressed in the adventitia on the first day after vascular injury compared to the expression levels in the media. Conversely, by the 14th day post-injury, Meox1 was extensively expressed more in the media and neointima than the adventitia. Analogous to the change of Meox1 in injured artery, Sca-1+ progenitor cells increased in the adventitia wall in a time-dependent manner and reached peak levels on the 7th day after injury. More importantly, this effect was abolished by Meox1 knockdown with shRNA. The enhanced expression of SDF-1α after vascular injury was associated with the markedly enhanced expression levels of Sca1+ progenitor cell, and these levels were relatively synchronously increased within neointima by the 7th day after vascular injury. These special effects were abolished by the knockdown of Meox1 with shRNA and inhibition of CXCR4 by its inhibitor, AMD3100. Finally, Meox1 concurrently regulated SDF-1α expressions in VSMC via activating CDC42, and CDC42 inhibition abolished these effects by its inhibitor, ZCL278. Also, Meox1 was involved in activation of the CXCR4 expression of Sca-1+ progenitor cells by CDC42.ConclusionsSpatio-temporal model of Meox1 expression regulates theSca-1+progenitor cell migration during the formation of the neointima through the synergistic effect of Rho/CDC42 and SDF-1α/CXCR4.

【 授权许可】

CC BY