ER[alpha] inhibited myocardin-induced differentiation in uterine fibroids

• Published in: Experimental cell research Vol. 350; no. 1; p. 73
• Main Authors: Liao, Xing-Hua, Li, Jun-Yan, Dong, Xiu-Mei, Wang, Xiuhong, Xiang, Yuan, Li, Hui, Yu, Cheng-Xi, Li, Jia-Peng, Yuan, Bai-Yin, Zhou, Jun, Zhang, Tong-Cun
• Format: Journal Article
• Language: English
• Published: New York Elsevier BV 01.01.2017
• Subjects: Cell growth; Fibroids; Protein expression
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2016.11.007

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 ER[alpha] 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 SM22[alpha] and alpha smooth muscle actin ([alpha]-SMA) in rat primary uterine smooth muscle cells (USMCs) and this effect was inhibited by ER[alpha]. Notably, we showed that, ER[alpha] induced expression of proliferation markers PCNA and ki-67 in rat primary USMCs. We also found ER[alpha] interacted with myocardin and formed complex to bind to CArG box and inhibit the SM22[alpha] promoter activity. Furthermore, ER[alpha] inhibited the transcription and expression of myocardin, and reduced the levels of transcription and expression of downstream target SM22[alpha], a SMC differentiation marker. Our data thus provided important and novel insights into how ER[alpha] and myocardin interact to control the cell differentiation and proliferation of USMCs. Thus, it may provide potential therapeutic target for uterine fibroids.