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

  • Yuko Kato
  • Utako Yokoyama
  • Takayuki Fujita
  • Masanari Umemura
  • Tetsuo Kubota
  • Yoshihiro Ishikawa
Original Paper
  • 65 Downloads

Abstract

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.

Keywords

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

Notes

Acknowledgements

The authors are grateful to Yuka Sawada (Yokohama City University) for histological analysis.

Funding sources

This study was funded by MEXT/JSPS KAKENHI (YK, JP17K08976; UY, JP17K19403, JP16H05358, JP15H05761; YI, JPH1605300), the Takeda Science Foundation (YK), the Japan Agency for Medical Research and Development (AMED) (YI, 66890007, 66891153), and the Kitsuen Research Foundation (YI, 71890005).

Supplementary material

Supplemental movie I. Epac1+/+-VSMC migration under stimulation with 10 ng/ml of bFGF. (MPG 887 kb)

Supplemental movie II. Epac1−/−-VSMC migration under stimulation with 10 ng/ml of bFGF. (MPG 885 kb)

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Copyright information

© The Physiological Society of Japan and Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Cardiovascular Research InstituteYokohama City UniversityYokohamaJapan
  2. 2.Department of ImmunopathologyTokyo Medical and Dental University, Graduate School of Medical and Dental SciencesTokyoJapan

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