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


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.
Yuge
Akitoshi
A
Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Yufu-shi, Oita, Japan.
Nasu
Kaei
K
Matsumoto
Harunobu
H
Nishida
Masakazu
M
Narahara
Hisashi
H
D000199:Actins / Q000378:metabolism; D000328:Adult; D000577:Amides / Q000494:pharmacology; D002454:Cell Differentiation; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D004715:Endometriosis / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D004717:Endometrium / Q000166:cytology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis / Q000209:etiology / Q000473:pathology*; D005782:Gels; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology; D017154:Stromal Cells / Q000166:cytology*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D054460:rho-Associated Kinases
D000199:Actins; D000577:Amides; D005782:Gels; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; D013778:Tetrazolium Salts; D013844:Thiazoles; C108830:Y 27632; D003094:Collagen; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; C022616:thiazolyl blue