The Canonical Wnt Signaling Transduction Pathway In The Pathogenesis Of Pelvic Organ Prolapse

BackgroundSeriously affecting women’s health and quality of life, pelvic organ prolapse (POP) with a higher incidence is considered as the common surgical indications in postmenopausal patients.Lots of proteins and pathways are reported to be involved in the pathogenesis of POP in which changes of the Wnt signaling pathway are related to the development of POP. In the present study, we will try to explore the role of Wnt signaling pathway-associated proteins (Wnt16, FZD5and β-catenin) in the proliferation and secretion of fibroblasts, which may be helpful for a better understanding of the disease.ObjectiveTo study the canonical Wnt signaling transduction pathway in the fibroblasts of uterosacral ligament of POP patients.MethodsFive patients with grade≥ⅢPOP and five with other benign gynecologic disorders as control were recruited in the study. Specimens were taken from the uterosacral ligaments and fibroblasts were cultured and purified. After confirmining of the fibroblasts cultured by immunohistochemical staining, we detected their growth and proliferation activity by MTT assay as well as the expression of MMP-2, Wnt16, FZD5and β-catenin by Western Blot.Result1. More than90%of the cells cultured were fibroblasts with vimentin positive while keratin negative.2. The growth and proliferation activity of fibroblasts in the POP group was significantly lower than the control group (P<0.01).3. The level of MMP-2and FZD5in the POP group was significantly higher than the control group (P<0.05and P<0.01, separately) while that of Wnt16, β-catenin was significantly lower in comparison with the control group (P<0.05)Conclusion1. The growth and proliferation activity of fibroblasts in the POP group was significantly lower than the control group.2. Elevated MMP-2in POP group may contribute to increased degradation of collagen, leading to POP.3. The canonical Wnt16signaling transduction pathway was inhibited in the fibroblasts of POP patients giving rise to lower growth and proliferation activity and reduced ability to secrete collagen. This pathway may be responsible to the changes of collagen state in the pelvic organ support structures which leaded to POP.