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Integrin-linked kinase improves uterine receptivity formation by activating Wnt/?-catenin signaling and up-regulating MMP-3/9 expression.


ABSTRACT: A receptive endometrium is a prerequisite for successful embryo implantation, and about one-third of repeated embryo implantation failure attribute to defective endometrial receptivity. Integrin-linked kinase (ILK), a 59kDa serine/threonine-protein kinase, plays a vital role in multiple cellular processes, including cell proliferation, apoptosis, and invasion. However, its role in endometrial receptivity is still unclear. In the current study, we demonstrated that ILK level was significantly downregulated in the serum of patients with unexplained infertility compared with healthy non-pregnancy. Functionally, ILK knockdown inhibited endometrial epithelial cells (EECs) proliferation and invasion, whereas ILK overexpression promoted endometrial EECs proliferation and invasion. ILK inhibition also repressed the adhesion rate of embryonic cells to EECs. In vivo studies further demonstrated that ILK inhibition suppressed endometrium receptivity formation and embryo implantation potential. Mechanistically, the downregulation of ILK inactivated Wnt/?-catenin signaling and thus resulted in the downregulation of MMP-3 and MMP-9 expression. Importantly, activation of Wnt/?-catenin signaling, partially recovered ILK inhibition-caused endometrium receptivity defects, and embryo implantation failure. Considered all the current data, it verified that the low expression of ILK exacerbates endometrial receptivity formation by inactivating Wnt/?-catenin signaling and decreasing the MMP-3/9 expression and indicated that ILK may be applied as an indicator of endometrial receptivity, and as a diagnostic and therapeutic target for infertility.

SUBMITTER: Chen Q 

PROVIDER: S-EPMC7344108 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Integrin-linked kinase improves uterine receptivity formation by activating Wnt/β-catenin signaling and up-regulating MMP-3/9 expression.

Chen Qian Q   Ni Ying Y   Han Mi M   Zhou Wen-Jie WJ   Zhu Xiao-Bin XB   Zhang Ai-Jun AJ  

American journal of translational research 20200615 6


A receptive endometrium is a prerequisite for successful embryo implantation, and about one-third of repeated embryo implantation failure attribute to defective endometrial receptivity. Integrin-linked kinase (ILK), a 59kDa serine/threonine-protein kinase, plays a vital role in multiple cellular processes, including cell proliferation, apoptosis, and invasion. However, its role in endometrial receptivity is still unclear. In the current study, we demonstrated that ILK level was significantly dow  ...[more]

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