Role of Activin-A and Myostatin and Their Signaling Pathway in Human Myometrial and Leiomyoma Cell Function
Role of Activin-A and Myostatin and Their Signaling Pathway in Human Myometrial and Leiomyoma Cell Function
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DOI：
10.1210/jc.2013-2623
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发表时间：
2014-05-01
影响因子：
5.8
通讯作者：
Ciarmela, Pasquapina
中科院分区：
文献类型：
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作者：
Islam, Md Soriful;Catherino, William H.;Ciarmela, Pasquapina
背景：子宫平滑肌瘤是绝经前妇女中非常常见的良性肿瘤，也是子宫切除术的最常见适应症。目的：本研究的目的是评估激活素A和肌生成抑制素及其信号通路在人子宫肌层和平滑肌瘤细胞中的作用。设计：本研究为实验室研究。（原代和细胞系）体外培养。该研究包括绝经前妇女谁是入院子宫肌瘤切除术或子宫切除术。干预措施：将原代子宫肌层和平滑肌瘤细胞和/或细胞系用激活素A（4 nM）和肌生长抑制素（4 nM）处理不同天数的间隔（测量增殖率）或30分钟（以测量信号分子）或48小时以通过实时PCR、蛋白质印迹和/或免疫细胞化学测量增殖标记物、细胞外基质mRNA和/或蛋白质表达。我们发现，激活素A和肌肉生长抑制素显着减少原代子宫肌层细胞的细胞增殖，但不是在平滑肌瘤细胞，如测量的CyQUANT细胞增殖检测试剂盒。在子宫肌层细胞中也观察到增殖细胞核抗原和Ki-67的表达减少，以响应激活素A和肌生长抑制素治疗。激活素A还显著增加原代平滑肌瘤细胞中纤连蛋白、胶原1A 1和多功能蛋白聚糖的mRNA表达。最后，我们发现，激活素A和肌肉生长抑制素激活Smad-2/3信号，但不影响ERK或p38信号在子宫肌层和平滑肌瘤celles.Conclusions：这项研究结果表明，激活素A和肌肉生长抑制素可以发挥抗增殖和/或纤维化的影响，这些细胞类型通过Smad-2/3信号。
Context: Uterine leiomyomas are highly prevalent benign tumors of premenopausal women and the most common indication for hysterectomy. However, the exact etiology of this tumor is not fully understood.Objective: The objective of the study was to evaluate the role of activin-A and myostatin and their signaling pathways in human myometrial and leiomyoma cells.Design: This was a laboratory study.Setting: Myometrial and leiomyoma cells (primary and cell lines) were cultured in vitro.Patients: The study included premenopausal women who were admitted to the hospital for myomectomy or hysterectomy.Interventions: Primary myometrial and leiomyoma cells and/or cell lines were treated with activin-A (4 nM) and myostatin (4 nM) for different days of interval (to measure proliferation rate) or 30 minutes (to measure signaling molecules) or 48 hours to measure proliferating markers, extracellular matrix mRNA, and/or protein expression by real-time PCR, Western blot, and/or immunocytochemistry.Results: We found that activin-A and myostatin significantly reduce cell proliferation in primary myometrial cells but not in leiomyoma cells as measured by a CyQUANT cell proliferation assay kit. Reduced expression of proliferating cell nuclear antigen and Ki-67 were also observed in myometrial cells in response to activin-A and myostatin treatment. Activin-A also significantly increased mRNA expression of fibronectin, collagen1A1, and versican in primary leiomyoma cells. Finally, we found that activin-A and myostatin activate Smad-2/3 signaling but do not affect ERK or p38 signaling in both myometrial and leiomyoma cells.Conclusions: This study results suggest that activin-A and myostatin can exert antiproliferative and/or fibrotic effects on these cell types via Smad-2/3 signaling.