Extra-nuclear activation of progesterone receptor in regulating arterial smooth muscle cell migration

Sung Po Hsu, Thay Hsiung Chen, Yu Pei Chou, Li Ching Chen, Chun Ting Kuo, Tong Sheng Lee, Jheng Jhe Lin, Nen Chun Chang, Wen Sen Lee

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

We previously showed that progesterone (P4) inhibits the proliferation of rat aortic smooth muscle cells (RASMC). Here, we further demonstrate that P4 at physiologic levels (5-500 nM) concentration-dependently inhibited migration of cultured RASMC. The effect is blocked by pretreatment with progesterone receptor (PR) antagonist, RU486. The P4-induced RASMC migration inhibition was through RhoA inactivation induced by cSrc-enhanced RhoA degradation. The P4-induced increases of phosphorylated Src (pSrc) and PR-pSrc complex in RASMC were observed mainly in the membrane fraction. Pre-treatment with a cSrc inhibitor (PP2) or cSrc antisense oligonucleotides prevented the P4-induced decreases of the protein levels of RhoA, phosphorylated FAK (p-FAK) and paxillin phosphorylaton and migration inhibition in RASMC. These findings expend our knowledge of the basis of P4's effect on vascular smooth muscle cell migration and highlight novel pathways of signaling transduction of P4 through PR-mediated nongenomic mechanisms.

Original languageEnglish
Pages (from-to)83-89
Number of pages7
JournalAtherosclerosis
Volume217
Issue number1
DOIs
Publication statusPublished - Jul 2011

Keywords

  • CSrc
  • Migration
  • Progesterone
  • RhoA
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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