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

Fingerprint

Progesterone Receptors
Smooth Muscle Myocytes
Cell Movement
rhoA GTP-Binding Protein
Cell Migration Inhibition
Paxillin
Antisense Oligonucleotides
Vascular Smooth Muscle
Progesterone
Membranes

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Extra-nuclear activation of progesterone receptor in regulating arterial smooth muscle cell migration. / Hsu, Sung Po; Chen, Thay Hsiung; Chou, Yu Pei; Chen, Li Ching; Kuo, Chun Ting; Lee, Tong Sheng; Lin, Jheng Jhe; Chang, Nen Chun; Lee, Wen Sen.

In: Atherosclerosis, Vol. 217, No. 1, 07.2011, p. 83-89.

Research output: Contribution to journalArticle

Hsu, Sung Po ; Chen, Thay Hsiung ; Chou, Yu Pei ; Chen, Li Ching ; Kuo, Chun Ting ; Lee, Tong Sheng ; Lin, Jheng Jhe ; Chang, Nen Chun ; Lee, Wen Sen. / Extra-nuclear activation of progesterone receptor in regulating arterial smooth muscle cell migration. In: Atherosclerosis. 2011 ; Vol. 217, No. 1. pp. 83-89.
@article{e9b628c5b0b1440abbc61bb956af78be,
title = "Extra-nuclear activation of progesterone receptor in regulating arterial smooth muscle cell migration",
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.",
keywords = "CSrc, Migration, Progesterone, RhoA, Vascular smooth muscle cells",
author = "Hsu, {Sung Po} and Chen, {Thay Hsiung} and Chou, {Yu Pei} and Chen, {Li Ching} and Kuo, {Chun Ting} and Lee, {Tong Sheng} and Lin, {Jheng Jhe} and Chang, {Nen Chun} and Lee, {Wen Sen}",
year = "2011",
month = "7",
doi = "10.1016/j.atherosclerosis.2011.02.051",
language = "English",
volume = "217",
pages = "83--89",
journal = "Atherosclerosis",
issn = "0021-9150",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

TY - JOUR

T1 - Extra-nuclear activation of progesterone receptor in regulating arterial smooth muscle cell migration

AU - Hsu, Sung Po

AU - Chen, Thay Hsiung

AU - Chou, Yu Pei

AU - Chen, Li Ching

AU - Kuo, Chun Ting

AU - Lee, Tong Sheng

AU - Lin, Jheng Jhe

AU - Chang, Nen Chun

AU - Lee, Wen Sen

PY - 2011/7

Y1 - 2011/7

N2 - 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.

AB - 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.

KW - CSrc

KW - Migration

KW - Progesterone

KW - RhoA

KW - Vascular smooth muscle cells

UR - http://www.scopus.com/inward/record.url?scp=79960206319&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960206319&partnerID=8YFLogxK

U2 - 10.1016/j.atherosclerosis.2011.02.051

DO - 10.1016/j.atherosclerosis.2011.02.051

M3 - Article

C2 - 21440892

AN - SCOPUS:79960206319

VL - 217

SP - 83

EP - 89

JO - Atherosclerosis

JF - Atherosclerosis

SN - 0021-9150

IS - 1

ER -