Cheng Jung-Chien, Chang Hsun-Ming, Fang Lanlan, Sun Ying-Pu, Leung Peter C K
Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, V5Z 4H4, Canada.
Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, V5Z 4H4, Canada; Reproductive Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
PLoS One. 2015 May 8;10(5):e0126532. doi: 10.1371/journal.pone.0126532. eCollection 2015.
Connective tissue growth factor (CTGF), which is also called CCN2, is a secreted matricellular protein. CTGF regulates various important cellular functions by interacting with multiple molecules in the microenvironment. In the ovary, CTGF is mainly expressed in granulosa cells and involved in the regulation of follicular development, ovulation and luteinization. TGF-β1 has been shown to up-regulate CTGF expression in rat and hen granulosa cells. However, the underlying molecular mechanisms of this up-regulation remain undefined. More importantly, whether the stimulatory effect of TGF-β1 on CTGF expression can be observed in human granulosa cells remains unknown. In the present study, our results demonstrated that TGF-β1 treatment up-regulates CTGF expression in both immortalized human granulosa cells and primary human granulosa cells. Using a siRNA-mediated knockdown approach and a pharmacological inhibitor, we demonstrated that the inhibition of Smad2, Smad3 or ERK1/2 attenuates the TGF-β1-induced up-regulation of CTGF. This study provides important insights into the molecular mechanisms that mediate TGF-β1-up-regulated CTGF expression in human granulosa cells.
结缔组织生长因子（CTGF），也称为CCN2，是一种分泌型基质细胞蛋白。CTGF通过与微环境中的多种分子相互作用来调节各种重要的细胞功能。在卵巢中，CTGF主要在颗粒细胞中表达，并参与卵泡发育、排卵和黄体化的调节。已表明TGF-β1可上调大鼠和母鸡颗粒细胞中CTGF的表达。然而，这种上调的潜在分子机制仍不清楚。更重要的是，TGF-β1对人颗粒细胞中CTGF表达的刺激作用是否能被观察到仍不清楚。在本研究中，我们的结果表明，TGF-β1处理可上调永生化人颗粒细胞和原代人颗粒细胞中CTGF的表达。使用siRNA介导的敲低方法和一种药理抑制剂，我们证明抑制Smad2、Smad3或ERK1/2可减弱TGF-β1诱导的CTGF上调。本研究为介导TGF-β1上调人颗粒细胞中CTGF表达的分子机制提供了重要见解。
