Tumor necrosis factor-α converting enzyme in the human placenta throughout gestation
Tumor necrosis factor-α converting enzyme in the human placenta throughout gestation
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DOI：
10.1177/1933719107310709
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发表时间：
2008-02-01
影响因子：
2.9
通讯作者：
Hsieh, T'sang-T'ang
中科院分区：
文献类型：
--
作者：
Hung, Tai-Ho;Chen, Szu-Fu;Hsieh, T'sang-T'ang
表皮生长因子受体配体如转化生长因子-α(TGF-α)、肝素结合的表皮生长因子样生长因子(HBEGF)和两用调节素(AREG)在植入过程中的胞外脱落被认为是重要的。肿瘤坏死因子-α转换酶(TACE)被认为是这些分子的主要脱水酶。本研究的目的是(1)研究TACE在人胎盘中的表达；(2)确定TACE与转化生长因子-α、HBEGF和AREG的表达之间的关系；(3)确定TACE是否介导了转化生长因子-α、HBEGF和AREG的脱落；(4)检测低氧对TACE表达的影响。通过对55例代表不同胎龄的绒毛标本的分析，发现TACE在整个妊娠过程中在胎盘中持续表达，且TACE水平与胎盘组织中TGF-α、HBEGF、AREG水平呈正相关。在绒毛组织培养中预先给予TACE抑制剂，或将TACE特异性小干扰RNA导入细胞滋养层细胞，可减少HBEGF和AREG的脱落。此外，低氧(2%O-2)可引起体外培养的绒毛组织和原代细胞滋养层细胞中TACE基因和蛋白的表达水平升高。这些结果表明，氧气调节TACE的表达，TACE可能在人类妊娠期胎盘发育中起重要作用。
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 arc (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.