Collagen gel contractility is enhanced in human endometriotic stromal cells: a possible mechanism underlying the pathogenesis of endometriosis-associated fibrosis.
Collagen gel contractility is enhanced in human endometriotic stromal cells: a possible mechanism underlying the pathogenesis of endometriosis-associated fibrosis.
复制标题
DOI：
10.1093/humrep/del485
复制
发表时间：
2007-04
影响因子：
6.1
通讯作者：
A. Yuge;K. Nasu;H. Matsumoto;M. Nishida;H. Narahara
中科院分区：
文献类型：
--
作者：
A. Yuge;K. Nasu;H. Matsumoto;M. Nishida;H. Narahara
背景过度纤维化常与子宫内膜异位症相关。为了评估子宫内膜异位症间质细胞（ECSCs）的细胞外基质收缩性在子宫内膜异位症相关纤维化发病机制中的作用，我们比较了培养的ECSCs与正常子宫内膜间质细胞的胶原凝胶收缩性。为了阐明ECSCs收缩胶原凝胶的机制，我们还评估了(+)-(R)-反式-4-（1-氨基乙基）- n -（4-吡啶基）环己anecarboxamide二盐酸一水合物（Y-27632）（一种选择性rho相关的卷曲形成蛋白激酶（ROCK）抑制剂）对ECSCs收缩胶原凝胶的影响。方法与结果与NESCs相比，ECSCs表现出增强的胶原凝胶收缩性。3D培养观察到内皮细胞的肌成纤维分化和纤维连接蛋白、RhoA、ROCK-I和ROCK-II蛋白表达的增加。Y-27632明显抑制ECSCs的胶原凝胶收缩性，无细胞毒性。结论：ECSCs中胶原收缩性增强与肌成纤维细胞分化、纤维连接蛋白表达增加和rho - rock介导的信号通路激活有关，这些都可能参与子宫内膜异位症相关纤维化的发病机制。这些结果表明，抑制rho - rock介导的信号通路可能为治疗这种疾病提供一种新的策略。此外，我们使用3D胶原凝胶培养的ECSCs实验系统将适用于评估子宫内膜异位症的新治疗方法。
BACKGROUND Excessive fibrosis is frequently associated with endometriosis. To evaluate the involvement of the extracellular matrix contractility of endometriotic stromal cells (ECSCs) in the pathogenesis of endometriosis-associated fibrosis, we compared the collagen gel contractility of cultured ECSCs with that of normal endometrial stromal cells. To clarify the mechanism underlying collagen gel contraction by ECSCs, we also evaluated the effect of (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride, monohydrate (Y-27632), a selective Rho-associated coiled-coil-forming protein kinase (ROCK) inhibitor, on the collagen gel contraction by ECSCs. METHODS AND RESULTS ECSCs showed enhanced collagen gel contractility in comparison with NESCs. Myofibroblastic differentiation and the increased expression of fibronectin, RhoA, ROCK-I and ROCK-II proteins were observed with ECSCs using the 3D culture. Y-27632 significantly inhibited the collagen gel contractility of ECSCs without cytotoxicity. CONCLUSIONS The present findings suggest that the enhanced collagen contractility in ECSCs is associated with myofibroblastic differentiation, the increased expression of fibronectin and the activation of the Rho-ROCK-mediated signalling pathway, all of which may be involved in the pathogenesis of endometriosis-associated fibrosis. These results suggest that the inhibition of the Rho-ROCK-mediated signalling pathway may provide a novel strategy for the treatment of this disease. In addition, our experimental system of ECSCs using 3D collagen gel culture would be suitable for evaluating novel treatments for endometriosis.