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Dynamic alterations in integrin α4 expression by hypoxia are involved in trophoblast invasion during early implantation
Author(s) -
Na KyuHwan,
Lee HyunJung,
Choi JongHo,
Eun JungWoo,
Nam SukWoo,
Yoon TaeKi,
Kim GiJin
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23398
Subject(s) - trophoblast , integrin , biology , microbiology and biotechnology , extracellular matrix , matrix metalloproteinase , downregulation and upregulation , cell migration , cell , placenta , fetus , pregnancy , biochemistry , genetics , gene
Implantation of the blastocyst into the maternal endometrium is mediated by a population of well‐differentiated primary cells of the placenta known as trophoblasts, which grow in an invasive and destructive fashion similar to tumor cells. Interactions between the endometrium and trophoblasts are regulated by a coordinated interplay of extracellular matrix (ECM) proteins secreted by the invading extravillous trophoblasts. Integrins act as adhesion receptors and mediate both cell–ECM and cell–cell interactions. However, the correlation between integrin expression and trophoblast invasion under hypoxia is unclear. Here, we analyzed the expression of integrins in HTR‐8/SVneo trophoblast cells exposed to hypoxic conditions in order to demonstrate an association between invasion activity and integrin expression in trophoblasts. Trophoblasts were examined by microarray analysis, RT‐PCR, western blotting, and zymography after 1% hypoxic treatment, and cell invasion was estimated. The dynamic expression of integrins and human matrix metalloproteinases (MMPs) was observed under hypoxic conditions. The invasiveness of trophoblasts cultured under 1% hypoxic conditions was significantly greater than that of trophoblasts cultured under normoxic conditions through alterations in MMP‐2 and ‐9 ( P < 0.05). Notably, integrin α4 expression during early hypoxia was negatively regulated by hypoxia‐inducible factor‐1alpha (HIF‐1alpha) expression in trophoblasts. The downregulation of integrin α4 expression by siRNA treatment controlled trophoblast invasion activity ( P < 0.05). Taken together, we suggest that dynamic changes in integrins, including those in integrin α4 expression by hypoxia, play a regulatory role in trophoblast invasion. These findings expand our understanding of the potential roles of integrin α4 in implantation. J. Cell. Biochem. 113: 685–694, 2012. © 2011 Wiley Periodicals, Inc.