Cheng Jung-Chien, Chang Hsun-Ming, Leung Peter C K
Department of Obstetrics and Gynaecology, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.
Endocrinology. 2017 Oct 1;158(10):3620-3628. doi: 10.1210/en.2017-00536.
Appropriate trophoblast invasion into the maternal endometrium is essential for successful human implantation and placentation. Connective tissue growth factor (CTGF), also known as CCN2, is a matricellular protein that is expressed in the placenta. Interestingly, the CTGF expression levels in the placenta and serum from patients with severe preeclampsia or fetal growth restriction are higher than those from healthy controls. However, to date, the role of CTGF in the regulation of trophoblast cell invasion remains unclear. Transforming growth factor-β1 (TGF-β1) is a potent stimulator of CTGF expression and has been shown to inhibit trophoblast cell invasiveness. However, whether CTGF mediates TGF-β1-inhibited human trophoblast cell invasion is unknown. In the present study, we show that treatment with TGF-β1 upregulates CTGF expression in a human trophoblast cell line, HTR-8/SVneo, and in primary human trophoblast cells. Our results also demonstrate that the SMAD2/3 signaling pathways are required for TGF-β1-induced upregulation of CTGF. Importantly, CTGF knockdown attenuates TGF-β1-inhibited cell invasion. Furthermore, cell invasiveness is decreased by treatment with recombinant CTGF. These results provide evidence that CTGF mediates TGF-β1-inhibited human trophoblast cell invasion.
适当的滋养层细胞侵入母体子宫内膜对于人类成功着床和胎盘形成至关重要。结缔组织生长因子（CTGF），也称为CCN2，是一种在胎盘中表达的基质细胞蛋白。有趣的是，重度子痫前期或胎儿生长受限患者胎盘和血清中的CTGF表达水平高于健康对照者。然而，迄今为止，CTGF在调节滋养层细胞侵袭中的作用仍不清楚。转化生长因子-β1（TGF-β1）是CTGF表达的有效刺激物，并且已被证明可抑制滋养层细胞的侵袭性。然而，CTGF是否介导TGF-β1抑制的人滋养层细胞侵袭尚不清楚。在本研究中，我们表明用TGF-β1处理可上调人滋养层细胞系HTR-8/SVneo和原代人滋养层细胞中的CTGF表达。我们的结果还表明，SMAD2/3信号通路是TGF-β1诱导的CTGF上调所必需的。重要的是，CTGF基因敲低减弱了TGF-β1抑制的细胞侵袭。此外，用重组CTGF处理可降低细胞侵袭性。这些结果提供了证据，证明CTGF介导TGF-β1抑制的人滋养层细胞侵袭。
