College of Animal Science and Technology, Nanjing Agricultural University, Weigang 1, Nanjing 210095, People's Republic of China.
Reproduction. 2011 May;141(5):643-51. doi: 10.1530/REP-10-0098. Epub 2011 Feb 3.
FSH plays a critical role in granulosa cell (GC) proliferation and steroidogenesis through modulation by factors including bone morphogenetic proteins family, which belongs to transforming growth factor β (TGFB) superfamily. TGFBs are the key factors in maintaining cell growth and differentiation in ovaries. However, the interaction of FSH and TGFB on the GCs' proliferation and steroidogenesis remains to be elucidated. In this study, we have investigated the role of SMAD4, a core molecule mediating the intracellular TGFB/SMAD signal transduction pathway, in FSH-mediated proliferation and steroidogenesis of porcine GCs. In this study, SMAD4 was knocked down using interference RNA in porcine GCs. Our results showed that SMAD4-siRNA causes specific inhibition of SMAD4 mRNA and protein expression after transfection. Knockdown of SMAD4 significantly inhibited FSH-induced porcine GC proliferation and estradiol production and changed the expression of cyclin D2, CDK2, CDK4, CYP19a1, and CYP11a1. Thus, these observations establish an important role of SMAD4 in the regulation of the response of porcine GCs to FSH.
卵泡刺激素（FSH）通过骨形态发生蛋白家族等因素的调节，在颗粒细胞（GC）增殖和类固醇生成中发挥关键作用，该家族属于转化生长因子β（TGFB）超家族。TGFBs 是维持卵巢中细胞生长和分化的关键因素。然而，FSH 和 TGFB 对 GCs 增殖和类固醇生成的相互作用仍有待阐明。在这项研究中，我们研究了 SMAD4 在 FSH 介导的猪 GCs 增殖和类固醇生成中的作用，SMAD4 是一种介导细胞内 TGFB/SMAD 信号转导途径的核心分子。在这项研究中，我们使用干扰 RNA 敲低了猪 GCs 中的 SMAD4。我们的结果表明，SMAD4-siRNA 转染后可特异性抑制 SMAD4 mRNA 和蛋白表达。SMAD4 的敲低显著抑制了 FSH 诱导的猪 GC 增殖和雌二醇的产生，并改变了细胞周期蛋白 D2、CDK2、CDK4、CYP19a1 和 CYP11a1 的表达。因此，这些观察结果确立了 SMAD4 在调节猪 GCs 对 FSH 反应中的重要作用。
