S100B is required for maintaining an intermediate state with double-positive Sca-1+ progenitor and vascular smooth muscle cells during neointimal formation

Stem Cell Research & Therapy

Shan Li¹  Shi-You Chen²  Jin-xuan Zhang³  Jun-Ming Tang³  Yu-wen Yan³  Xing-Yuan Li³  Yan Wu³  Fei Zheng⁴  Yu Liu⁴  Lei Zhang⁴  Ye Yuan⁴  Jia-Ning Wang⁴  Ling-Yun Guo⁴  Xin Liu⁵ 

[1]Department of Biochemistry, School of Basic Medicine Science, Hubei University of Medicine

[2]Department of Physiology & Pharmacology, The University of Georgia

[3]Department of Physiology, School of Basic Medicine Science, Hubei University of Medicine

[4]Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine

[5]Laboratory Animal Center, Hubei University of Medicine

关键词: S100B;    Sca-1;    Intermediate state;    Neointima;    SDF-1α;    NF-κB;   

DOI  :  10.1186/s13287-019-1400-0

来源: DOAJ

【 摘 要 】

Abstract Introduction Accumulation of vascular smooth muscle cells (VSMCs) within the neointimal region is a hallmark of atherosclerosis and vessel injury. Evidence has shown that Sca-1-positive (Sca-1+) progenitor cells residing in the vascular adventitia play a crucial role in VSMC assemblages and intimal lesions. However, the underlying mechanisms, especially in the circumstances of vascular injury, remain unknown. Methods and results The neointimal formation model in rats was established by carotid artery balloon injury using a 2F-Forgaty catheter. Most Sca-1+ cells first appeared at the adventitia of the vascular wall. S100B expressions were highest within the adventitia on the first day after vessel injury. Along with the sequentially increasing trend of S100B expression in the intima, media, and adventitia, respectively, the numbers of Sca-1+ cells were prominently increased at the media or neointima during the time course of neointimal formation. Furthermore, the Sca-1+ cells were markedly increased in the tunica media on the third day of vessel injury, SDF-1α expressions were obviously increased, and SDF-1α levels and Sca-1+ cells were almost synchronously increased within the neointima on the seventh day of vessel injury. These effects could effectually be reversed by knockdown of S100B by shRNA, RAGE inhibitor (SPF-ZM1), or CXCR4 blocker (AMD3100), indicating that migration of Sca-1+ cells from the adventitia into the neointima was associated with S100B/RAGE and SDF-1α/CXCR4. More importantly, the intermediate state of double-positive Sca-1+ and α-SMA cells was first found in the neointima of injured arteries, which could be substantially abrogated by using shRNA for S100B or blockade of CXCR4. S100B dose-dependently regulated SDF-1α expressions in VSMCs by activating PI3K/AKT and NF-κB, which were markedly abolished by PI3K/AKT inhibitor wortmannin and enhanced by p65 blocker PDTC. Furthermore, S100B was involved in human umbilical cord-derived Sca-1+ progenitor cells’ differentiation into VSMCs, especially in maintaining the intermediate state of double-positive Sca-1+ and α-SMA. Conclusions S100B triggered neointimal formation in rat injured arteries by maintaining the intermediate state of double-positive Sca-1+ progenitor and VSMCs, which were associated with direct activation of RAGE by S100B and indirect induction of SDF-1α by activating PI3K/AKT and NF-κB.

【 授权许可】

Unknown