Functional antagonism between high-temperature requirement protein A (HtrA) family members regulates trophoblast cell invasion
Date Issued
2014
Date
2014
Author(s)
Chen, Yao-Yu
Abstract
Human trophoblast invasion of decidualized endometrium is essential for placentation and is tightly regulated and involves decidua-trophoblastic interaction. High-temperature requirement A4 (HtrA4) is a secreted serine protease highly expressed in the invasive extravillous trophoblasts and promotes decidua-trophoblastic interaction. In contrast, both HtrA1 and HtrA3 have been shown to inhibit placental cell invasion. Here we provide evidence that decidua-secreted HtrA1 and HtrA3 antagonize HtrA4-mediated placental cell invasion. We demonstrated that HtrA1 and HtrA3 interact with and degrade HtrA4, thereby inhibit placental cell invasion. HtrA1 and HtrA3 expression is upregulated by decidualization in endometrial stromal and epithelial cells, T-HESCs and Ishikawa cells, respectively. By RNA interference, we demonstrated that HtrA1 and HtrA3 are responsible for the suppression of HtrA4-expressing JAR placental cell invasion by conditioned media of decidualized T-HESCs and Ishikawa cells. Co-culture of the HtrA4-expressing JAR cells with decidualized T-HESC or Ishikawa monolayer also impairs HtrA4-mediated 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 placental cell invasion through physical and functional interaction between HtrA family members.
Subjects
滋養層細胞
胎盤
HtrA4
細胞入侵
Type
thesis
File(s)![Thumbnail Image]()
Loading...
Name
ntu-103-R01b46005-1.pdf
Size
23.32 KB
Format
Adobe PDF
Checksum
(MD5):f1ee2d38af6b895775478067dc2f28f9