Epac1 deficiency inhibits basic fibroblast growth factor-mediated vascular smooth muscle cell migration

The journal of physiological sciences

article

Yuko Kato¹  Utako Yokoyama¹  Takayuki Fujita¹  Masanari Umemura¹  Tetsuo Kubota²  Yoshihiro Ishikawa¹ 

[1] Cardiovascular Research Institute, Yokohama City University;Department of Immunopathology, Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences

关键词: Exchange protein activated by cAMP 1;    Intimal thickening;    Basic fibroblast growth factor;    Vascular smooth muscle cells;    Migration;   

DOI  :  10.1007/s12576-018-0631-7

来源: Springer

【 摘 要 】

Vascular smooth muscle cell (VSMC) migration and the subsequent intimal thickening play roles in vascular restenosis. We previously reported that an exchange protein activated by cAMP 1 (Epac1) promotes platelet-derived growth factor (PDGF)-induced VSMC migration and intimal thickening. Because basic fibroblast growth factor (bFGF) also plays a pivotal role in restenosis, we examined whether Epac1 was involved in bFGF-mediated VSMC migration. bFGF-induced lamellipodia formation and migration were significantly decreased in VSMCs obtained from Epac1−/− mice compared to those in Epac1+/+-VSMCs. The bFGF-induced phosphorylation of Akt and glycogen synthase kinase 3β (GSK3β), which play a role in bFGF-induced cell migration, was attenuated in Epac1−/−-VSMCs. Intimal thickening induced by the insertion of a large wire was attenuated in Epac1−/− mice, and was accompanied by the decreased phosphorylation of GSK3β. These data suggest that Epac1 deficiency attenuates bFGF-induced VSMC migration, possibly via Akt/GSK3β pathways.

【 授权许可】

Unknown