Graduate Institute of Medical Sciences, Medical College, Taipei Medical University, Taipei, Taiwan.
Atherosclerosis. 2011 Jul;217(1):83-9. doi: 10.1016/j.atherosclerosis.2011.02.051. Epub 2011 Mar 10.
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.
我们之前曾表明孕激素（P4）可抑制大鼠主动脉平滑肌细胞（RASMC）的增殖。在这里，我们进一步证明 P4 在生理浓度（5-500 nM）下可浓度依赖性地抑制培养的 RASMC 的迁移。该作用可被孕激素受体（PR）拮抗剂 RU486 预处理所阻断。P4 诱导的 RASMC 迁移抑制作用是通过 cSrc 增强 RhoA 降解引起的 RhoA 失活介导的。在 RASMC 中观察到 P4 诱导的磷酸化 Src（pSrc）和 PR-pSrc 复合物增加主要存在于膜部分。用 cSrc 抑制剂（PP2）或 cSrc 反义寡核苷酸预处理可防止 P4 诱导的 RhoA、磷酸化 FAK（p-FAK）和桩蛋白磷酸化水平以及 RASMC 迁移抑制的降低。这些发现扩展了我们对 P4 对血管平滑肌细胞迁移影响的基础的认识，并强调了 P4 通过 PR 介导的非基因组机制进行信号转导的新途径。
