Functional antagonism between high temperature requirement protein a (HtrA) family members regulates trophoblast invasion

Yao Yu Chen, Pei Yun Chuang, Chie Pein Chen, Yueh Ho Chiu, Hsiao Fan Lo, Mei Leng Cheong, Jyun Yuang Huang, Pao Lin Kuo, Hungwen Chen

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12 Citations (Scopus)

Abstract

Human trophoblast invasion of decidualized endometrium is essential for placentation and is tightly regulated and involves trophoblast-decidual cell interaction. High temperature requirement A4 (HtrA4) is a secreted serine protease highly expressed in the invasive extravillous trophoblasts that invade decidua. In contrast, both HtrA1 and HtrA3 have been shown to inhibit trophoblast invasion. Here we provide evidence that decidua-secreted HtrA1 and HtrA3 antagonize HtrA4-mediated trophoblast invasion. We demonstrated that HtrA1 and HtrA3 interact with and degrade HtrA4 and thereby inhibit tro-phoblast- like JAR cell invasion. Specifically, HtrA1 and HtrA3 expression is up-regulated under decidualization conditions in endometrial stromal and epithelial cells, T-HESCs and Ishikawa cells, respectively. Conditioned media from these two cell lines after decidualization treatment suppress HtrA4-expressing JAR cell invasion in an HtrA1- or HtrA3-dependent manner. Co-culture of the HtrA4-expressing JAR cells with decidualization stimuli-treated T-HESC or Ishikawa monolayer also impairs JAR cell invasion, which can be reversed by HtrA1 or HtrA3 knockdown, supporting that HtrA1 and HtrA3 are crucial for trophoblast-decidual cell interaction in the control of trophoblast invasion. Our study reveals a novel regulatory mechanism of trophoblast invasion through physical and functional interaction between HtrA family members.

Original languageEnglish
Pages (from-to)22958-22968
Number of pages11
JournalJournal of Biological Chemistry
Volume289
Issue number33
DOIs
Publication statusPublished - 2014 Aug 15

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Chen, Y. Y., Chuang, P. Y., Chen, C. P., Chiu, Y. H., Lo, H. F., Cheong, M. L., Huang, J. Y., Kuo, P. L., & Chen, H. (2014). Functional antagonism between high temperature requirement protein a (HtrA) family members regulates trophoblast invasion. Journal of Biological Chemistry, 289(33), 22958-22968. https://doi.org/10.1074/jbc.M114.576744