Increased expression of p21-activated kinase 4 in adenomyosis and its regulation of matrix metalloproteinase-2 and-9 in endometrial cells
- Authors
- Yi, Kyong Wook; Kim, Sung Hoon; Ihm, Hyo Jin; Oh, Young Sang; Chae, Hee Dong; Kim, Chung-Hoon; Kang, Byung Moon
- Issue Date
- 4월-2015
- Publisher
- ELSEVIER SCIENCE INC
- Keywords
- P21-activated kinase 4 (Pak4); adenomyosis; endometrium; matrix metalloproteinase (MMP); nuclear factor kappa-B (NF-kappa B)
- Citation
- FERTILITY AND STERILITY, v.103, no.4, pp.1089 - U303
- Indexed
- SCIE
SCOPUS
- Journal Title
- FERTILITY AND STERILITY
- Volume
- 103
- Number
- 4
- Start Page
- 1089
- End Page
- U303
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/93914
- DOI
- 10.1016/j.fertnstert.2014.12.124
- ISSN
- 0015-0282
- Abstract
- Objective: To 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. Design: Experimental study using human samples and cell lines. Setting: University 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-kappa B) 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-kappa B 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-kappa B activation and Pak4 expression, which was obviously decreased by the NF-kappa B inhibitor pyrrolidinedithiocarbamate. Conclusion(s): Our results suggest that Pak4 is regulated by NF-kappa B 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. (C) 2015 by American Society for Reproductive Medicine.
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