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Progesterone Inhibits Endothelial Cell Migration Through Suppression of the Rho Activity Mediated by cSrc Activation
Author(s) -
Lee TongSheng,
Lin JhenJhe,
Huo YenNien,
Lee WenSen
Publication year - 2015
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25101
Subject(s) - rhoa , cell migration , microbiology and biotechnology , signal transduction , focal adhesion , paxillin , chemistry , rho associated protein kinase , endothelial stem cell , biology , cell , biochemistry , in vitro
ABSTRACT We previously showed that progesterone (P4) could inhibit the proliferation of human umbilical venous endothelial cells (HUVECs) through the p53‐dependent pathway. In the present study, we further demonstrated that P4 at physiologic levels (5–500 nM) concentration‐dependently inhibited migration of HUVECs. This effect was blocked by pre‐treatment with the P4 receptor (PR) agonist‐antagonist, RU486, suggesting that the P4‐induced migration inhibition in HUVECs was through the PR‐mediated signaling pathway. Western blot analyses demonstrated that the levels of RhoA and Rac‐1 protein were reduced in the P4‐treated HUVECs. P4 also inhibited the membrane translocation of RhoA and Rac‐1 protein. Moreover, the P4‐induced migration inhibition in HUVECs was prevented by over‐expression of the constitutively active RhoA construct (RhoA V14). However, pre‐treatment with the ROCK (a kinase associated with RhoA for transducing RhoA signaling) inhibitor, Y27632, abolished the over‐expression of RhoA‐induced prevention effect on the P4‐induced migration inhibition in HUVECs. These data suggest that the inhibition of Rho GTPases might account for the P4‐induced migration inhibition of HUVECs. Pre‐treatment with the cSrc inhibitor, PP2, prevented the P4‐induced migration inhibition in HUVEC. The levels of phosphorylated focal adhesion kinase (FAK) and paxillin protein were also decreased by P4 treatment. Taken together, these results suggest that suppression of the Rho‐mediated pathway might be involved in the signal transduction leading to the inhibition of cell migration caused by P4 in HUVECs. J. Cell. Biochem. 116: 1411–1418, 2015. © 2015 Wiley Periodicals, Inc.