Abstract
BackgroundDuring the development and progression of endometriotic lesions, excess fibrosis may lead to scarring, chronic pain, and altered tissue function. However, the cellular and molecular mechanisms of fibrosis in endometriosis remain to be clarified.ObjectivesThe objective of the present study was to investigate whether the Wnt/β-catenin signaling pathway was involved in regulating the cellular and molecular mechanisms of fibrosis in endometriosis in vitro and to evaluate whether fibrosis could be prevented by targeting the Wnt/β-catenin pathway in a xenograft model of endometriosis in immunodeficient nude mice.MethodsSeventy patients (40 with and 30 without endometriosis) with normal menstrual cycles were recruited. In vitro effects of small-molecule antagonists of the Tcf/β-catenin complex (PKF 115-584 and CGP049090) on fibrotic markers (alpha smooth muscle actin, type I collagen, connective tissue growth factor, fibronectin) and collagen gel contraction were evaluated in endometrial and endometriotic stromal cells from patients with endometriosis. In vitro effects of activation of the Wnt/β-catenin signaling pathway by treatment with recombinant Wnt3a on profibrotic responses were evaluated in endometrial stromal cells of patients without endometriosis. The effects of CGP049090 treatment on the fibrosis of endometriotic implants were evaluated in a xenograft model of endometriosis in immunodeficient nude mice.ResultsTreatment with PKF 115-584 and CGP049090 significantly decreased the expression of alpha smooth muscle actin, type I collagen, connective tissue growth factor and fibronectin mRNAs in both endometriotic and endometrial stromal cells with or without transforming growth factor-β1 stimulation. Both endometriotic and endometrial stromal cell-mediated contraction of collagen gels was significantly decreased by treatment with PKF 115-584 and CGP049090 as compared to that of untreated cells. The animal experiments showed that CGP049090 prevented the progression of fibrosis and reversed established fibrosis in endometriosis.ConclusionAberrant activation of the Wnt/β-catenin pathway may be involved in mediating fibrogenesis in endometriosis.
Highlights
Endometriosis, a common cause of infertility and pelvic pain, is defined as the presence of endometrial glands and stroma in extra-uterine sites [1]
Β-Catenin small interfering RNA (siRNA) significantly lowered FN mRNA, whereas the expression of αSMA, Col-I, and connective tissue growth factor (CTGF) transcripts was not altered by βcatenin siRNA, compared to control transfection, in both endometriotic (Figure 1A) and endometrial (Figure 1B) stromal cells
transforming growth factor (TGF)-β1 stimulation increased the expression of αSMA, Col-I, CTGF, and FN transcripts, and this effect was significantly attenuated by β-catenin siRNA in endometriotic (Figure 1A) and endometrial (Figure 1B) stromal cells
Summary
Endometriosis, a common cause of infertility and pelvic pain, is defined as the presence of endometrial glands and stroma in extra-uterine sites [1]. During the development and progression of endometriotic lesions, excess fibrosis may lead to scarring, chronic pain, and altered tissue function, all of which are characteristics of this disease [2,3]. In vitro effects of small-molecule antagonists of the Tcf/β-catenin complex (PKF 115-584 and CGP049090) on fibrotic markers (alpha smooth muscle actin, type I collagen, connective tissue growth factor, fibronectin) and collagen gel contraction were evaluated in endometrial and endometriotic stromal cells from patients with endometriosis. Results: Treatment with PKF 115-584 and CGP049090 significantly decreased the expression of alpha smooth muscle actin, type I collagen, connective tissue growth factor and fibronectin mRNAs in both endometriotic and endometrial stromal cells with or without transforming growth factor-β1 stimulation. Conclusion: Aberrant activation of the Wnt/β-catenin pathway may be involved in mediating fibrogenesis in endometriosis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
