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

Kyong Wook Yi, Sung Hoon Kim, Hyo Jin Ihm, Young Sang Oh, Hee Dong Chae, Chung Hoon Kim, Byung Moon Kang

Research output: Contribution to journalArticle

14 Citations (Scopus)

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-κB) 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-κB 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-κB activation and Pak4 expression, which was obviously decreased by the NF-κB inhibitor pyrrolidinedithiocarbamate. Conclusion(s): Our results suggest that Pak4 is regulated by NF-κB 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.

Original languageEnglish
Pages (from-to)1089-1097.e2
JournalFertility and Sterility
Volume103
Issue number4
DOIs
Publication statusPublished - 2015 Jan 1

Fingerprint

p21-Activated Kinases
Adenomyosis
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
NF-kappa B
Small Interfering RNA
Transfection
Endometrium
Carcinoma in Situ
Endometriosis
Stromal Cells
Cervix Uteri
Research Design

Keywords

  • Adenomyosis
  • Endometrium
  • Matrix metalloproteinase (MMP)
  • Nuclear factor kappa-B (NF-κB)
  • P21-activated kinase 4 (Pak4)

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynaecology

Cite this

Increased expression of p21-activated kinase 4 in adenomyosis and its regulation of matrix metalloproteinase-2 and -9 in endometrial cells. / Yi, Kyong Wook; Kim, Sung Hoon; Ihm, Hyo Jin; Oh, Young Sang; Chae, Hee Dong; Kim, Chung Hoon; Kang, Byung Moon.

In: Fertility and Sterility, Vol. 103, No. 4, 01.01.2015, p. 1089-1097.e2.

Research output: Contribution to journalArticle

Yi, Kyong Wook ; Kim, Sung Hoon ; Ihm, Hyo Jin ; Oh, Young Sang ; Chae, Hee Dong ; Kim, Chung Hoon ; Kang, Byung Moon. / Increased expression of p21-activated kinase 4 in adenomyosis and its regulation of matrix metalloproteinase-2 and -9 in endometrial cells. In: Fertility and Sterility. 2015 ; Vol. 103, No. 4. pp. 1089-1097.e2.
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T1 - Increased expression of p21-activated kinase 4 in adenomyosis and its regulation of matrix metalloproteinase-2 and -9 in endometrial cells

AU - Yi, Kyong Wook

AU - Kim, Sung Hoon

AU - Ihm, Hyo Jin

AU - Oh, Young Sang

AU - Chae, Hee Dong

AU - Kim, Chung Hoon

AU - Kang, Byung Moon

PY - 2015/1/1

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N2 - 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-κB) 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-κB 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-κB activation and Pak4 expression, which was obviously decreased by the NF-κB inhibitor pyrrolidinedithiocarbamate. Conclusion(s): Our results suggest that Pak4 is regulated by NF-κB 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.

AB - 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-κB) 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-κB 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-κB activation and Pak4 expression, which was obviously decreased by the NF-κB inhibitor pyrrolidinedithiocarbamate. Conclusion(s): Our results suggest that Pak4 is regulated by NF-κB 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.

KW - Adenomyosis

KW - Endometrium

KW - Matrix metalloproteinase (MMP)

KW - Nuclear factor kappa-B (NF-κB)

KW - P21-activated kinase 4 (Pak4)

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