Hung Tai-Ho, Chen Szu-Fu, Hsieh Ching-Chang, Hsu Jenn-Jeih, Li Meng-Jen, Yeh Yi-Lin, Hsieh T'sang-T'ang
Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taipei, Taiwan.
Reprod Sci. 2008 Feb;15(2):195-209. doi: 10.1177/1933719107310709.
Ectodomain shedding of epidermal growth factor receptor ligands such as transforming growth factor- alpha (TGF-alpha), heparin-binding epidermal growth factor-like growth factor (HBEGF), and amphiregulin (AREG) is considered to be important during implantation. Tumor necrosis factor-alpha converting enzyme (TACE) has been suggested as the major sheddase for these molecules. The objectives of this study are (1) to characterize the expression of TACE in the human placenta throughout gestation; (2) to determine the association between the expression of TACE with TGF-alpha, HBEGF, and AREG; (3) to ascertain whether TACE mediates TGF-alpha, HBEGF, and AREG shedding; and (4) to examine the effect of hypoxia on the expression of TACE. By analyzing a total of 55 villous samples representing different gestational ages, the authors found that TACE was continuously expressed in the placentas throughout gestation and that the levels of TACE were positively correlated with the levels of TGF-alpha, HBEGF, and AREG. Preadministration of a TACE inhibitor in villous explant cultures or transfection of cytotrophoblastic cells with TACE-specific small interference RNA decreased the shedding of HBEGF and AREG. Moreover, hypoxia (2% O(2)) caused an increase in the levels of TACE mRNA and protein in villous explants and primary cytotrophoblastic cells in vitro. These results indicate that oxygen regulates the expression of TACE and that TACE may be important for placental development during human pregnancy.
表皮生长因子受体配体（如转化生长因子-α （TGF-α）、肝素结合表皮生长因子样生长因子（HBEGF）和双调蛋白（AREG））的胞外域脱落被认为在着床过程中很重要。肿瘤坏死因子-α转化酶（TACE）被认为是这些分子的主要脱落酶。本研究的目的是：（1） 描述TACE在整个妊娠期人胎盘中的表达特征；（2） 确定TACE的表达与TGF-α、HBEGF和AREG之间的关联；（3） 确定TACE是否介导TGF-α、HBEGF和AREG的脱落；（4） 研究缺氧对TACE表达的影响。通过分析总共55个代表不同孕周的绒毛样本，作者发现TACE在整个妊娠期的胎盘中持续表达，且TACE水平与TGF-α、HBEGF和AREG水平呈正相关。在绒毛外植体培养物中预先给予TACE抑制剂或用TACE特异性小干扰RNA转染细胞滋养层细胞可减少HBEGF和AREG的脱落。此外，缺氧（2% O₂）导致体外绒毛外植体和原代细胞滋养层细胞中TACE mRNA和蛋白水平升高。这些结果表明，氧调节TACE的表达，且TACE可能对人类妊娠期间的胎盘发育很重要。
