title: Dynamic alterations in integrin α4 expression by hypoxia are involved in trophoblast invasion during early implantation.
abstract: 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.
authors: Department of Biomedical Science, CHA University, Seoul 135-081, Republic of Korea.
authors: Kyu-Hwan
authors: KH
authors: Na
authors: Hyun-Jung
authors: HJ
authors: Lee
authors: Jong-Ho
authors: JH
authors: Choi
authors: Jung-Woo
authors: JW
authors: Eun
authors: Suk-Woo
authors: SW
authors: Nam
authors: Tae-Ki
authors: TK
authors: Yoon
authors: Gi-Jin
authors: GJ
authors: Kim
mesh_terms: D015687:Cell Hypoxia; D002460:Cell Line; D002465:Cell Movement; D010064:Embryo Implantation; D015870:Gene Expression; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006801:Humans; D039441:Integrin alpha4 / Q000235:genetics / Q000378:metabolism*; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: D016023:Integrins; D039441:Integrin alpha4