Mitofusin2 regulates the proliferation and function of fibroblasts: The possible mechanisms underlying pelvic organ...

The present study aimed to investigate the effects of Mitofusin2 (Mfn2) on the proliferation of human uterosacral ligament fibroblasts and on the expression of procollagen. We also aimed to identify the possible signal transduction pathway involved in the development of pelvic organ prolapse (POP). For this purpose, uterosacral ligaments were harvested from POP and non‑pelvic organ prolapse (NPOP) patients for fibroblast culture. Cellular proliferation and the cell cycle were assessed following transduction with lentiviral vectors for the overexpression and suppression of Mfn2. The expression levels of the proteins Mfn2, procollagens, phosphoprotein 21 wild‑type p53 activating fragment (p21Waf1), cyclin‑dependent kinase 2 (CDK2), extracellular signal‑regulated kinase1/2 (ERK1/2) and rapidly accelerated fibrosarcoma‑1 (Raf‑1) were examined. Overexpression of Mfn2 resulted in the decreased proliferation of cells and the induction of G0/G1 phase arrest. Concomitantly, the relative expression levels of procollagen proteins, CDK2 and the phosphorylation levels of ERK1/2 and Raf‑1 proteins were notably decreased, while the levels of the p21waf1 protein were increased in the Mfn2 overexpressing group. Opposing results were reported cells following Mfn2 silencing via RNA interference. The results of the present study indicated that the cell cycle of the fibroblasts, their cellular proliferation and the levels of the procollagen proteins could be inhibited via the Ras‑Raf‑ERK axis as a result of the increased levels of Mfn2 during the development of POP.