Collagen gel contractility is enhanced in human endometriotic stromal cells: a possible mechanism underlying the pathogenesis of endometriosis-associated fibrosis

Abstract

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.

A chemical biology screen reveals a role for Rab21-mediated control of actomyosin contractility in fibroblast-driven cancer invasion

“…Myosin activity is largely controlled by the phosphorylation of MLC, which can be performed by numerous kinases including the RhoA-regulated kinases ROCK1 and ROCK2 (Olson and Sahai, 2009). Both ROCK and MLC function are required for matrix remodelling by fibroblasts (Gaggioli et al, 2007;Honjo et al, 2007;Yuge et al, 2007).…”

Simvastatin inhibits the proliferation and the contractility of human endometriotic stromal cells: a promising agent for the treatment of endometriosis

“…We have established a three-dimensional (3-D) collagen gel culture system with human endometriotic stromal cells as a model of fibrosis formation in endometriosis (5,6). Endometriotic stromal cells were cultured in floating collagen lattices to induce the reorganization and compaction of collagen fibers, resulting in the contraction of the collagen gels.…”

“…This culture system provided a model of mechanically relaxed tissue with low tensile strength comparable with that in the early stages of development of endometriotic lesions. Using this model, we demonstrated that endometriotic stromal cells cultured in floating 3-D collagen gel exhibit a more enhanced contractile profile and greater ability to differentiate into a myofibroblast phenotype than do normal endometrial stromal cells (5,6). Activation of the Ras homology (Rho)-Rho-associated coiled-coil-forming protein kinase (ROCK)-mediated pathway in endometriotic stromal cells may be involved in this phenomenon (5,6).…”

“…To assess the effects of simvastatin on the contractility of endometriotic stromal cells, cellular collagen gel contraction assays were performed as previously described (5,18). In the presence of 10% fetal bovine serum, untreated endometriotic stromal cells showed significant collagen gel contractility (74.9% AE 0.7% decrease in gel surface area after 48 hours vs. 0 hours for controls).…”

“…Research on endometriotic stromal cell biology in 3-D collagen matrices offers new opportunities to gain a better understanding of the reciprocal and adaptive interactions that take place between cells and the surrounding matrix in a tissue-like environment (5). Such interactions are integrated with the regulation of endometriotic tissue morphogenesis and the dynamics that characterize endometriosis-associated fibrosis.…”