Regulation of P21-activated kinase-4 by progesterone and tumor necrosis factor-α in human endometrium and its increased expression in advanced-stage endometriosis

孕酮和肿瘤坏死因子-α对人子宫内膜中P21活化激酶-4的调节及其在晚期子宫内膜异位症中的表达增加

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作者:Sung Hoon Kim, So Ra Kim, Hyo Jin Ihm, Young Sang Oh, Hee Dong Chae, Chung-Hoon Kim, Byung Moon Kang

Conclusion

These findings suggest that Pak4 is regulated by progesterone and TNF-α in endometrial cells and that the increased expression of Pak4 might lead to the establishment and progression of endometriosis by enhanced cellular viability and invasiveness in endometrial cells.

Methods

Pak4 expression was analyzed using immunohistochemistry and Western blot analysis. Viability and invasiveness were assayed after transfection of endometrial cells with Pak4 small interfering RNA.

Objective

The aim was to evaluate the effects of sex steroids and proinflammatory cytokines on the Pak4 expression in endometrial cells along with the functional change caused by inhibition of Pak4 expression as well as to see whether the Pak4 expression is altered in endometriosis.

Results

The Pak4 expression was significantly decreased in the stromal cells during the secretory phase as well as by in vitro treatment with progesterone. The immunoreactivity of Pak4 was significantly increased in the eutopic endometrium as well as in the ovarian endometriotic cyst of women with endometriosis compared with the control subjects. TNF-α induced a significant increase in the Pak4 expression in endometrial cells in vitro, whereas IL-1β had no effects. Transfection of endometrial cells with Pak4 small interfering RNA led to a significant decrease in viability and invasiveness in endometrial cells.

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