Correlations between Mitofusin 2 Expression in Fibroblasts and Pelvic Organ Prolapse: An In vitro Study.

BACKGROUND: Both Mitofusin 2 (Mfn2) and pelvic organ prolapse (POP) are related to aging. The aim of the present study was to investigate the variations of Mfn2 expression in the uterosacral ligaments of patients with and/or without POP and their correlations with the expression of procollagen.

METHODS: Fibroblasts were cultured using tissue specimens that were harvested from the uterosacral ligaments of POP and non-POP (NPOP) patients (n = 10 for each group) from September 2016 to December 2016. The Cell Counting Kit-8 (CCK-8) assay was used to compare the differences in cell proliferation between the two groups. Relative quantitative reverse transcription-polymerase chain reaction and Western blotting assays were employed to assess the differences in the mRNA and protein expression levels of Mfn2 and procollagen 1A1/1A2/3A1 between the two groups. The changes in procollagen expression were assessed following the downregulation of Mfn2 in the POP group using RNAi. The data were assessed with independent sample t- test or general linear model univariate analysis using the SPSS 13.0 software.

RESULTS: The results from CCK-8 assay indicated that cell viability in the POP group was significantly lower compared with that of the NPOP group (td5, 7, 9, 11= -5.925, -6.851, -9.129, and -9.661, respectively, all P < 0.001, from D5 to D11). The mRNA and protein expression levels of Mfn2 in the cultured fibroblasts of the POP group were significantly higher compared with those of the NPOP group (mRNA: t = 2.425, P = 0.032; protein: t = 2.392, P = 0.037, respectively), whereas only the expression levels of procollagen 1A1/1A2/3A1 were significantly higher in the NPOP group (mRNA: t = -2.165, P1A1 = 0.041; t = -2.741, P1A2 = 0.026; t = -2.147, P3A1 = 0.045, respectively; protein: t = -2.418, P1A1 = 0.029; t = -2.405, P1A2 = 0.033; t = -2.470, P3A1 = 0.012, respectively). The expression levels of procollagen in the POP group increased following the downregulation of Mfn2.

CONCLUSIONS: The proliferation rate and cell viability of the fibroblasts in the POP group were significantly lower compared with those in the NPOP group. In the POP fibroblasts, Mfn2 expression was increased, while procollagen expression was decreased.