OBJECTIVE To investigate the mechanisms underlying the dual effects of estrogen on vascular smooth muscle cells (VSMC). METHODS MTT assay, ELISA, flow cytometry and Western analysis were used to investigate the effects of 17beta-estradiol (E(2)) on proliferation, apoptosis, cell cycle progression, ERK and p38 activities of subcultured rat VSMC with or without chemical block of MEK or p38 kinases. RESULTS E(2)-promoted VSMC proliferation was accompanied with an increased phosphorylation of ERK1/2, which could be blocked by MEK inhibitor U0126; the E(2)-induced VSMC apoptosis, which appeared mainly in the G2/M phase, was related with the activation of p38 and could be blocked by p38 inhibitor SB203580. More interestingly, MEK inhibition in E(2)-treated VSMC led to an enhanced p38 phosphorylation and a shift of apoptosis from G2/M phase-predominant to G0/G1 phase-predominant; whereas block of p38 increased the E(2)-induced ERK1/2 phosphorylation and proliferation of the VSMC. This reciprocal phenomenon was related with cross-talk between ERK and p38 pathways which might be mediated by MKP-1 and PP2A. The effects of E(2) on proliferation and apoptosis, and their related pathways could be separately induced by the specific agonists of estrogen receptor (ER) alpha and beta alone and inhibited or eliminated by the ER blocker ICI 182,780. CONCLUSION The dual effects of estrogen on VSMC involve concurrent activations of ERK and p38 pathways by ER alpha and beta respectively, and the fates of VSMC are determined by the dynamic balance between these two pathways.

中文翻译：

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血管平滑肌细胞对雌激素的反应取决于ERK和p38 MAPK途径活性之间的平衡。

目的探讨雌激素对血管平滑肌细胞（VSMC）双重作用的潜在机制。方法采用MTT法，ELISA法，流式细胞术和Western分析法研究17β-雌二醇（E（2））对有或无化学阻断作用的大鼠VSMC继代培养的VSMC增殖，凋亡，细胞周期进程，ERK和p38活性的影响。 MEK或p38激酶。结果E（2）促进的VSMC增殖伴随着ERK1 / 2磷酸化的增加，这可以被MEK抑制剂U0126阻断。E（2）诱导的VSMC凋亡主要出现在G2 / M期，与p38的活化有关，并可能被p38抑制剂SB203580阻断。更有趣的是 E（2）处理的VSMC中的MEK抑制导致增强的p38磷酸化和凋亡从G2 / M期为主向G0 / G1期为主；而p38的阻滞增加了VSMC的E（2）诱导的ERK1 / 2磷酸化和增殖。这种相互关系与ERK和p38途径之间的串扰有关，这可能是由MKP-1和PP2A介导的。E（2）对增殖和凋亡的影响及其相关途径可以单独由雌激素受体（ER）α和β的特异性激动剂诱导，并由ER阻滞剂ICI 182,780抑制或消除。结论雌激素对VSMC的双重作用涉及分别通过ERα和β同时激活ERK和p38途径，而VSMC的命运取决于这两种途径之间的动态平衡。