Bercina Candoso1, Maria J Meneses2, Marco G Alves2, Mário Sousa2,3, Pedro F Oliveira2,4,5. 1. Department of Urogynecology, Centro Hospitalar do Porto-Centro Materno Infantil do Norte, Porto, Portugal. 2. Department of Microscopy, Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar (ICBAS) and Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Porto, Portugal. 3. Center for Reproductive Genetics Professor Alberto Barros, Porto, Portugal. 4. Department of Genetics, Faculty of Medicine, University of Porto, Porto, Portugal. 5. i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
Abstract
AIMS: We aimed to assess the alterations in specific molecular mechanisms associated with collagenolysis and their correlation in cases of stress urinary incontinence (SUI) by urethral hypermobility (UH) and by intrinsic sphincter deficiency (ISD). METHODS: We evaluated the messenger RNA (mRNA) expression of matrix metalloproteinases (MMP1, MMP2, and MMP9), specific tissue inhibitors of metalloproteinases (TIMPs), and associated proteins (TIMP1, TIMP2, and α-2-macroglobulin [A2McG]) in the suburethral tissue of women with SUI (half with SUI by UH and half with SUI by ISD) by reverse-transcriptase quantitative polymerase chain reaction and determined the correlations of the expression of these proteins on each pathological condition. RESULTS: In the suburethral tissue, we found significantly altered MMP2 mRNA levels, being higher in women with ISD than in those with UH. Still, MMP1 and MMP9 exhibited a tendency to a higher expression in women with ISD. Concerning the TIMPs expression, no significant statistical differences were found between women with UH and ISD. When evaluating the MMP/TIMP ratios, we found significant statistical differences between MMP9/TIMP1 and MMP9/A2McG. In fact, the correlations of the expression MMP9 with TIMP1 and A2McG were lost for women with UH. The ratios between MMP1/TIMP1 and MMP1/A2McG were similar, although there was a tendency of higher ratio in ISD for MMP2/TIMP2 and MMP2/A2McG. CONCLUSION: Our results point toward higher collagenolysis in the suburethral tissue of women with SUI by ISD.
AIMS: We aimed to assess the alterations in specific molecular mechanisms associated with collagenolysis and their correlation in cases of stress urinary incontinence (SUI) by urethral hypermobility (UH) and by intrinsic sphincter deficiency (ISD). METHODS: We evaluated the messenger RNA (mRNA) expression of matrix metalloproteinases (MMP1, MMP2, and MMP9), specific tissue inhibitors of metalloproteinases (TIMPs), and associated proteins (TIMP1, TIMP2, and α-2-macroglobulin [A2McG]) in the suburethral tissue of women with SUI (half with SUI by UH and half with SUI by ISD) by reverse-transcriptase quantitative polymerase chain reaction and determined the correlations of the expression of these proteins on each pathological condition. RESULTS: In the suburethral tissue, we found significantly altered MMP2 mRNA levels, being higher in women with ISD than in those with UH. Still, MMP1 and MMP9 exhibited a tendency to a higher expression in women with ISD. Concerning the TIMPs expression, no significant statistical differences were found between women with UH and ISD. When evaluating the MMP/TIMP ratios, we found significant statistical differences between MMP9/TIMP1 and MMP9/A2McG. In fact, the correlations of the expression MMP9 with TIMP1 and A2McG were lost for women with UH. The ratios between MMP1/TIMP1 and MMP1/A2McG were similar, although there was a tendency of higher ratio in ISD for MMP2/TIMP2 and MMP2/A2McG. CONCLUSION: Our results point toward higher collagenolysis in the suburethral tissue of women with SUI by ISD.