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.
authors: Graduate Institute of Medical Sciences, Medical College, Taipei Medical University, Taipei, Taiwan.
authors: Sung-Po
authors: SP
authors: Hsu
authors: Thay-Hsiung
authors: TH
authors: Chen
authors: Yu-Pei
authors: YP
authors: Chou
authors: Li-Ching
authors: LC
authors: Chen
authors: Chun-Ting
authors: CT
authors: Kuo
authors: Tong-Sheng
authors: TS
authors: Lee
authors: Jheng-Jhe
authors: JJ
authors: Lin
authors: Nen-Chun
authors: NC
authors: Chang
authors: Wen-Sen
authors: WS
authors: Lee
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D001158:Arteries / Q000166:cytology*; D002448:Cell Adhesion; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D015735:Mifepristone / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D016376:Oligonucleotides, Antisense / Q000235:genetics; D051419:Paxillin / Q000235:genetics; D010766:Phosphorylation; D051381:Rats; D011980:Receptors, Progesterone / Q000235:genetics*; D013347:Subcellular Fractions / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D016376:Oligonucleotides, Antisense; D051419:Paxillin; D011980:Receptors, Progesterone; D015735:Mifepristone; D019061:src-Family Kinases