ERα inhibited myocardin-induced differentiation in uterine fibroids

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• 作者：Xing-Hua Liao^a ; ^b ; ¹ ; ^{xinghualiao@hotmail.com} ; Jun-Yan Li^d ; ¹ ; Xiu-Mei Dong^a ; ^f ; Xiuhong Wang^e ; Yuan Xiang^a ; Hui Li^a ; Cheng-Xi Yu^a ; Jia-Peng Li^a ; Bai-Yin Yuan^a ; Jun Zhou^a ; ^c ; ^{zhoujun@wust.edu.cn} ; Tong-Cun Zhang^a ; ^b ; ^{zhangtongcun@wust.edu.cn}
• 关键词：USMC ; uterine smooth muscle cells ; α-SMA ; alpha smooth muscle actin ; PBS ; phosphate-buffered saline ; H&E ; hematoxylin and eosin ; DAPI ; 4&prime ; 6&prime ; -diamidino-2-phenylindole ; RT-PCR ; reverse-transcription polymerase chain reaction ; qRT-PCR ; quantitative real-time RT-PCR ; ChIP ; chromatin immunoprecipitation ; SERMs ; selective estrogen receptor modulators ; ERE ; estrogen receptor binding element ; ER ; estrogen receptors
• 刊名：Experimental Cell Research
• 出版年：2017
• 出版时间：1 January 2017
• 年：2017
• 卷：350
• 期：1
• 页码：73-82
• 全文大小：1319 K
• 卷排序：350

文摘

Uterine fibroids, also known as uterine leiomyomas, are a benign tumor of the human uterus and the commonest estrogen-dependent benign tumor found in women. Myocardin is an important transcriptional regulator in smooth and cardiac muscle development. The role of myocardin and its relationship with ERα in uterine fibroids have barely been addressed. We noticed that the expression of myocardin was markedly reduced in human uterine fibroid tissue compared with corresponding normal or adjacent myometrium tissue. Here we reported that myocardin induced the transcription and expression of differentiation markers SM22α and alpha smooth muscle actin (α-SMA) in rat primary uterine smooth muscle cells (USMCs) and this effect was inhibited by ERα. Notably, we showed that, ERα induced expression of proliferation markers PCNA and ki-67 in rat primary USMCs. We also found ERα interacted with myocardin and formed complex to bind to CArG box and inhibit the SM22α promoter activity. Furthermore, ERα inhibited the transcription and expression of myocardin, and reduced the levels of transcription and expression of downstream target SM22α, a SMC differentiation marker. Our data thus provided important and novel insights into how ERα and myocardin interact to control the cell differentiation and proliferation of USMCs. Thus, it may provide potential therapeutic target for uterine fibroids.