title: ERα inhibited myocardin-induced differentiation in uterine fibroids.
abstract: 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.
authors.affiliation: Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065, PR China; Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China. Electronic address: xinghualiao@hotmail.com.
authors.forename: Xing-Hua
authors.initials: XH
authors.lastname: Liao
authors.affiliation: Henan Vocational College of Applied Technology, Zhengzhou 450042, PR China.
authors.forename: Jun-Yan
authors.initials: JY
authors.lastname: Li
authors.affiliation: Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065, PR China; Yuncheng County People's Hospital, Shandong 274700, PR China.
authors.forename: Xiu-Mei
authors.initials: XM
authors.lastname: Dong
authors.affiliation: Xianning Central Hospital, Department of Obstetrics and Gynecology, Xianning, Hubei 437100, PR China.
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065, PR China.
authors.forename: Cheng-Xi
authors.initials: CX
authors.lastname: Yu
authors.affiliation: Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065, PR China.
authors.forename: Jia-Peng
authors.initials: JP
authors.lastname: Li
authors.affiliation: Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065, PR China.
authors.forename: Bai-Yin
authors.initials: BY
authors.lastname: Yuan
authors.affiliation: Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065, PR China; School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, PR China. Electronic address: zhoujun@wust.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065, PR China; Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China. Electronic address: zhangtongcun@wust.edu.cn.
authors.forename: Tong-Cun
authors.initials: TC
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007889:Leiomyoma / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D026362:Serum Response Factor / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism / Q000494:pharmacology*; D000099251:Myocardin
chemical_list: D047628:Estrogen Receptor alpha; D009687:Nuclear Proteins; D026362:Serum Response Factor; D015534:Trans-Activators; D000099251:Myocardin
keywords: Differentiation and proliferation; ERα; Myocardin; Uterine fibroids; Uterine smooth muscle cell (USMC)