Tumor necrosis factor-α converting enzyme in the human placenta throughout gestation

Tai Ho Hung, Szu Fu Chen, Ching Chang Hsieh, Jenn Jeih Hsu, Meng Jen Li, Yi Lin Yeh, T'sang T.ang Hsieh*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

15 Scopus citations

Abstract

Ectodomain shedding of epidermal growth factor receptor ligands such as transforming growth factor-α (TGF-α), heparin-binding epidermal growth factor-like growth factor (HBEGF), and amphiregulin (AREG) is considered to be important during implantation. Tumor necrosis factor-α 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-α, HBEGF, and AREG; (3) to ascertain whether TACE mediates TGF-α, 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-α, 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% O2) 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.

Original languageEnglish
Pages (from-to)195-209
Number of pages15
JournalReproductive Sciences
Volume15
Issue number2
DOIs
StatePublished - 02 2008

Keywords

  • Amphiregulin
  • Heparin-binding epidermal growth factor-like growth factor
  • Placenta
  • Transforming growth factor-α
  • Tumor necrosis factor-α converting enzyme

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