Increased expression of p21-activated kinase 4 in adenomyosis and its regulation of matrix metalloproteinase-2 and -9 in endometrial cells

Kyong Wook Yi, Yi KW, Sung Hoon Kim, Kim SH, Ihm HJ, Hyo Jin Ihm, Oh YS, Young Sang Oh, Hee Dong Chae, Chae HD, Chung‐Hoon Kim, Kim CH, Chung-Hoon Kim, Kang BM, Byung Moon Kang
Fertility and sterility · 2015 · vol. 103(4) , pp. 1089–1097.e2 · doi:10.1016/j.fertnstert.2014.12.124 · PMID:25637478 · W2005242007
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This study investigated the role of p21-activated kinase 4 in adenomyosis, finding its increased expression in affected tissues and its regulation of matrix metalloproteinase-2 and -9 in endometrial cells.

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Abstract

ObjectiveTo investigate the expression of p21-activated kinase 4 (Pak4) in both adenomyotic foci and the eutopic endometrium of women with adenomyosis, and whether the activities of matrix metalloproteinases (MMPs)-2 and -9 are regulated by Pak4 in endometrial cells.DesignExperimental study using human samples and cell lines.SettingUniversity hospital.Patient(s)Thirty-nine patients with histologic evidence of adenomyosis, and 34 patients with carcinoma in situ of the uterine cervix without adenomyosis or endometriosis.Intervention(s)Immunohistochemistry, zymography after transfection with Pak4 small interfering RNA (siRNA), and western blot analyses after nuclear factor kappa-B (NF-кB) inhibitor treatment.Main outcome measure(s)The Pak4 immunoreactivity of women with vs. without adenomyosis was compared semiquantitatively. The activities of MMP-2 and -9 were analyzed in eutopic endometrial stromal cells and Ishikawa cells after transfection with Pak4 siRNA. The Pak4 expression was evaluated in endometrial cells after treatment with NF-кB inhibitor.Result(s)Pak4 immunoreactivity was increased in adenomyotic foci and in the eutopic endometrium of women with adenomyosis. Transfection of endometrial cells with Pak4 siRNA led to significant decreases of MMP-2 and -9 activities. In vitro treatment of endometrial cells with tumor necrosis factor-alpha caused a significant increase of NF-кB activation and Pak4 expression, which was obviously decreased by the NF-кB inhibitor pyrrolidinedithiocarbamate.Conclusion(s)Our results suggest that Pak4 is regulated by NF-кB and that increased Pak4 expression can lead to development of adenomyosis by enhancing the invasiveness of endometrial cells through regulation of MMP-2 and -9 activities.

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Condition tags

adenomyosis

MeSH descriptors

Adenomyosis Endometrium Matrix Metalloproteinase 2 Matrix Metalloproteinase 9 p21-Activated Kinases p21-Activated Kinases Adenomyosis Adenomyosis Adenomyosis Adult Cell Movement Cell Movement Cell Movement Cells, Cultured Endometrium Endometrium Enzyme Activation Enzyme Activation Female Humans

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