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D eath R eceptor 6 is E pigenetically S ilenced by H istone D eacetylation in E ndometriosis and P romotes the P athogenesis of E ndometriosis
Author(s) -
Kai Kentaro,
Nasu Kaei,
Kawano Yukie,
Aoyagi Yoko,
Tsukamoto Yoshiyuki,
Hijiya Naoki,
Abe Wakana,
Okamoto Mamiko,
Moriyama Masatsugu,
Narahara Hisashi
Publication year - 2013
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.12155
Subject(s) - endometriosis , stromal cell , cancer research , gene knockdown , medicine , pathogenesis , apoptosis , downregulation and upregulation , receptor , histone deacetylase , histone , biology , gene , biochemistry
Problem The purpose of this study is to evaluate the involvement of death receptor ( DR ) 6 in the pathogenesis of endometriosis. Methods of study Endometriotic cyst stromal cells ( ECSC s) and normal endometrial stromal cells ( NESC s) were isolated from ovarian endometriotic tissues and the eutopic endometrial tissues, respectively. The effect of valproic acid ( VPA ) on the DR 6 expression in ECSC s was examined. The roles of DR 6 in NESC proliferation and apoptosis were investigated with DR 6 si RNA transfection. The distribution of DR 6 protein in ovarian endometriotic tissues and normal proliferative‐phase endometrium was examined by immunohistochemistry. The expression of DR 6 m RNA and protein in ECSC s and NESC s was also examined. Results Death receptor 6 expression was attenuated in ECSC s and in endometriotic tissues, and its expression was upregulated by VPA stimulation. VPA treatment resulted in an accumulation of acetylated histone H 4 in the promoter region of the DR 6 gene. DR 6 knockdown directed the stimulation of cell proliferation and the resistance to apoptosis in NESC s. Conclusion The present findings suggested that DR6 is involved in the pathogenesis of endometriosis by creating the proliferative and anti‐apoptotic characteristics of endometriosis. The results also suggest that histone deacetylase inhibitors are promising agents for the treatment of endometriosis.