Semaphorin-3E attenuates neointimal formation via suppressing VSMCs migration and proliferation
Semaphorin-3E attenuates neointimal formation via suppressing VSMCs migration and proliferation
复制标题
Semaphorin-3E 通过抑制 VSMC 迁移和增殖来减弱新内膜形成
DOI：
10.1093/cvr/cvx190
复制
发表时间：
2017-12
影响因子：
10.8
通讯作者：
Hu Bo
中科院分区：
文献类型：
--
作者：
Wu Jie Hong;Li Yanan;Zhou Yi Fan;Haslam James;Elvis Opoku Nana;Mao Ling;Xia Yuan Peng;Hu Bo
Aims
The migration and proliferation of vascular smooth muscle cells (VSMCs) are crucial events in the neointimal formation, a hallmark of atherosclerosis and restenosis. Semaphorin3E (Sema3E) has been found to be a critical regulator of cell migration and proliferation in many scenarios. However, its role on VSMCs migration and proliferation is unclear. This study aimed to investigate the effect of Sema3E on VSMCs migration, proliferation and neointimal formation, and explore possible mechanisms.
Methods and results
We found that the expression of Sema3E was progressively decreased during neointimal formation in a carotid ligation model. H&E-staining showed lentivirus-mediated overexpression of Sema3E in carotid ligation area attenuated neointimal formation. Immunofluorescence staining showed that the receptor (PlexinD1) of Sema3E was expressed in vascular walls. In cultured mouse VSMCs, Sema3E inhibited VSMCs migration and proliferation via plexinD1 receptor. The inhibitory effect was mediated, at least in part, by inactivating Rap1-AKT signalling pathways in VSMCs. Moreover, we found that PDGFBB down-regulated the expression of Sema3E in VSMCs and Sema3E notably inhibited the expression of PDGFB in endothelial cells. In addition, the number of Sema3E-positive VSMCs was diminished in plaques of atherosclerotic patients. Results from a public GEO microarray database showed a negative correlation between Sema3E and PDGFB transcriptional levels in the human plaques examined.
Conclusion
Our study demonstrates that Sema3E/plexinD1 inhibits proliferation and migration of VSMCs via inactivation of Rap1-AKT signalling pathways. The mutual inhibition between PDGF-BB and Sema3E after vascular injury plays a critical role in the process of neointimal formation.
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影响因子：
11.8
作者：
Gitler, AD;Lu, MM;Epstein, JA
通讯作者：
Epstein, JA
DOI：
10.1073/pnas.87.11.4284
发表时间：
1990-06-01
影响因子：
11.1
作者：
KITAYAMA, H;MATSUZAKI, T;NODA, M
通讯作者：
NODA, M
影响因子：
64.8
作者：
Zhang L;Zhang S;Yao J;Lowery FJ;Zhang Q;Huang WC;Li P;Li M;Wang X;Zhang C;Wang H;Ellis K;Cheerathodi M;McCarty JH;Palmieri D;Saunus J;Lakhani S;Huang S;Sahin AA;Aldape KD;Steeg PS;Yu D
通讯作者：
Yu D
影响因子：
15.9
作者：
Casazza, Andrea;Finisguerra, Veronica;Tamagnone, Luca
通讯作者：
Tamagnone, Luca
影响因子：
14.2
作者：
Movassagh, Hesam;Shan, Lianyu;Gounni, Abdelilah S.
通讯作者：
Gounni, Abdelilah S.