Progesterone enhances vascular endothelial cell migration via activation of focal adhesion kinase

Journal of Cellular and Molecular Medicine

Shuhui Zheng¹  Jinghe Huang¹  Kewen Zhou¹  Qiuling Xiang¹  Yaxing Zhang¹  Zhi Tan¹  Tommaso Simoncini²  Xiaodong Fu¹ 

[1]Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China

[2]Molecular and Cellular Gynecological Endocrinology Laboratory (MCGEL), Department of Reproductive Medicine and Child Development, University of Pisa, Pisa, Italy

关键词: progesterone;    vascular endothelial cells;    focal adhesion kinase;    actin cytoskeleton;    cell movement;   

DOI  :  10.1111/j.1582-4934.2011.01305.x

来源: Wiley

【 摘 要 】

Abstract

The mechanisms of progesterone on endothelial cell motility are poorly investigated. Previously we showed that progesterone stimulated endothelial cell migration via the activation of actin-binding protein moesin, leading to actin cytoskeleton remodelling and the formation of cell membrane structures required for cell movement. In this study, we investigated the effects of progesterone on the formation of focal adhesion complexes, which provide anchoring sites for cell movement. In cultured human umbilical endothelial cells, progesterone enhanced focal adhesion kinase (FAK) phosphorylation at Tyr³⁹⁷ in a dose- and time-dependent manner. Several signalling inhibitors interfered with progesterone-induced FAK activation, including progesterone receptor (PR) antagonist ORG 31710, specific c-Src kinase inhibitor PP2, phosphatidylinosital-3 kinase (PI3K) inhibitor wortmannin as well as ρ-associated kinase (ROCK-2) inhibitor Y27632. It suggested that PR, c-Src, PI3K and ROCK-2 are implicated in this action. In line with this, we found that progesterone rapidly promoted c-Src/PI3K/Akt activity, which activated the small GTPase RhoA/ρ-associated kinase (ROCK-2) complex, resulting in FAK phosphorylation. In the presence of progesterone, endothelial cells displayed enhanced horizontal migration, which was reversed by small interfering RNAs abrogating FAK expression. In conclusion, progesterone promotes endothelial cell movement via the rapid regulation of FAK. These findings provide new information on the biological actions of progesterone on human endothelial cells that are relevant for vascular function.

【 授权许可】

Unknown   
© 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd