Jiangsu Diabetes Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 # HanKou Road, Nanjing, Jiangsu 210093, People's Republic of China.
Mol Cell Endocrinol. 2010 Feb 5;315(1-2):74-80. doi: 10.1016/j.mce.2009.09.018. Epub 2009 Sep 26.
Estrogen shows a vasoprotective role through inhibiting the proliferation and migration of vascular smooth muscle cells (VSMCs). The mechanism underlying the effect of estrogen, however, is not completely understood. Here, we explored the role of peroxisome proliferator-activated receptor-gamma (PPARgamma) coactivator-1alpha (PGC-1alpha) in estrogen-mediated vasoprotection. Firstly, we showed that oleic acid (OA) decreased PGC-1alpha expression while stimulating VSMC proliferation and migration. In contrast, administration of VSMCs with 17beta-estradiol (E(2), 1 or 10nM) significantly restored OA-decreased PGC-1alpha expression, treatment with 10nM E(2) almost completely abolished OA-induced VSMC proliferation and migration. Secondly, by using PGC-1alpha siRNA, the inhibitory effect of E(2) on VSMC growth is strongly reduced via suppressing PGC-1alpha expression, indicating that E(2) may exert its role through restoring PGC-1alpha. Finally, E(2) (10nM) treatment inhibits OA-induced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, however, suppression of PGC-1alpha expression abolishes this inhibitory effect of E(2). Our findings demonstrate for the first time that in OA-stimulated rat VSMCs, treatment with E(2) (1 or 10nM) diminishes VSMC proliferation and migration via restoring OA-decreased PGC-1alpha expression. This observation offers a novel molecular basis of the vasoprotective effect of estrogen.
雌激素通过抑制血管平滑肌细胞（VSMCs）的增殖和迁移发挥血管保护作用。然而，雌激素作用的机制尚不完全清楚。在这里，我们探讨了过氧化物酶体增殖物激活受体-γ（PPARγ）共激活因子-1α（PGC-1α）在雌激素介导的血管保护中的作用。首先，我们表明油酸（OA）降低了 PGC-1α 的表达，同时刺激了 VSMC 的增殖和迁移。相比之下，用 17β-雌二醇（E（2），1 或 10nM）处理 VSMCs 可显著恢复 OA 降低的 PGC-1α 表达，用 10nM E（2）处理几乎完全消除了 OA 诱导的 VSMC 增殖和迁移。其次，通过使用 PGC-1α siRNA，通过抑制 PGC-1α 的表达，强烈降低了 E（2）对 VSMC 生长的抑制作用，表明 E（2）可能通过恢复 PGC-1α 发挥其作用。最后，E（2）（10nM）处理抑制 OA 诱导的细胞外信号调节激酶 1/2（ERK1/2）磷酸化，然而，抑制 PGC-1α 的表达消除了 E（2）的这种抑制作用。我们的研究结果首次表明，在 OA 刺激的大鼠 VSMCs 中，用 E（2）（1 或 10nM）处理可通过恢复 OA 降低的 PGC-1α 表达来减少 VSMC 的增殖和迁移。这一观察结果为雌激素的血管保护作用提供了新的分子基础。
