Objective: To explore the effects of canonical Wnt signaling transduction pathway on the proliferation and secretion of fibroblasts of uterosacral ligament so as to elucidate the pathogenic mechanism of pelvic organ prolapse (POP).
Methods: Five patients with grade ≥Ш POP and five with other benign gynecologic disorders as control were recruited. Specimens were taken from uterosacral ligaments and fibroblasts were cultured and purified. After the confirmation of cultured fibroblasts by immunohistochemical staining, their growth and proliferation activity were detected by thiazolyl blue tetrazolium bromide (MTT) assay and the expressions of matrix metal proteinase-2 (MMP-2), Wnt16, FZD5 and β-catenin by Western blot.
Results: (1) Over 90% of the cultured cells were fibroblasts of vimentin positive and keratin negative. (2) The growth and proliferation activity of fibroblasts were significantly lower in the POP group than those in the control group (P<0.01). (3) The levels of MMP-2 and FZD5 in the POP group were significantly higher than those in the control group (P<0.05 and P<0.01 respectively) while those of Wnt16 and β-catenin were significantly lower than the control group (both P<0.05).
Conclusions: Canonical Wnt16 signaling transduction pathway becomes inhibited in the fibroblasts of POP patients resulting in lower growth and proliferation activity and reduced secretion of collagen. Elevated MMP-2 contributes to the increased degradation of collagen. And MMP-2 and Wnt16 signaling transduction pathway may be important factors for the changes of collagen state in pelvic organ support structures leading ot POP.