Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033377 (prolapse)
 11,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to investigate quantitative mRNA expression of matrix metalloproteinases MMP-1, MMP-2, MMP-9, and their inhibitors, the tissue inhibitors of metalloproteinases TIMP-1, TIMP-2 and TIMP-3, in vaginal wall tissue from women with stress urinary incontinence compared to continent controls. Vaginal wall tissues were obtained from 7 women with stress urinary incontinence/severe pelvic prolapse and 15 continent controls. RNA was then extracted and quantified. Quantitative competitive reverse transcription (QC-RT-PCR) was carried out with oligonucleotide primers to quantify MMP-1, MMP-2, MMP-9, TIMP-1, TIMP-2 and TIMP-3 mRNA expression. Stress continent women demonstrated a significant decrease in TIMP-1 and mRNA expression (P = 0.03). There was no difference in TIMP-2, TIMP-3, MMP-2 or MMP-9 mRNA expression between stress incontinent women and controls. However, MMP-1 mRNA expression was significantly increased (P = 0.05) in the incontinent group and the MMP-1/TIMP-1 ratio (P = 0.04) was consistent with increased collagen degradation in the stress incontinence. Stress incontinent women demonstrated an increase in MMP-1 mRNA expression and a decrease in the inhibitor TIMP-1 mRNA expression. Both these findings are consistent with increased collagen breakdown as a pathologic etiology of incontinence.
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PMID:Collagen metabolism and turnover in women with stress urinary incontinence and pelvic prolapse. 1205 87

The uterosacral ligaments are an important part of the pelvic support system and connective tissue alterations are thought to contribute to the development of pelvic organ prolapse (POP). The objective of this study was to compare the expression of matrix metalloproteinases (MMPs) 1 and 2 in these ligaments in women with and without POP. We analyzed the tissue samples obtained from left and/or right uterosacral ligaments of 17 women with POP and 18 controls by immunohistochemistry. There was no difference in MMP-1 expression between women with POP and those without. In contrast, the MMP-2 expression was significantly related to the presence of POP (p=0.004) rather than to age or parity. There was no difference in MMP-1 and MMP-2 expression between left and right uterosacral ligaments in women with POP compared to controls. Our findings strongly indicate that increased MMP-2 expression in uterosacral ligaments is associated with POP.
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PMID:Increased expression of matrix metalloproteinase 2 in uterosacral ligaments is associated with pelvic organ prolapse. 1634 61

Pelvic organ prolapse (POP) is a common disorder that can disturb the health and quality of life of females. However, the basic pathophysiology and underlying mechanism of POP are not fully understood. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been reported to be associated with the onset and development of POP. In the present study, to characterize the differential expression profile of MMPs and TIMPs in female patients with and without POP, a total of 72 POP patients were sampled as a patient group and 72 non-POP patients that underwent hysterectomy due to benign tumors were sampled as a control group. Immunohistochemistry and polymerase chain reaction analysis were used to detect the expression levels of MMP-1, -2, -3 and -9 as well as TIMP-1 protein and mRNA in the anterior vaginal wall tissues. The expression levels of MMP-1, -2, -3 and -9 in the patient group were found to be significantly higher than those in the control group. By contrast, TIMP-1 expression levels in the patient group were significantly lower than those in the control group. Correlational analysis revealed a significantly positive correlation among the expression levels of MMP-2, -3 and -9. TIMP-1 expression levels were significantly negatively correlated with the expression levels of MMP-3 and -9. In addition, the expression levels of MMP-1 exhibited a positive correlation with those of MMP-2, -3 and -9, but a negative correlation with those of TIMP-1. The results demonstrated that the increased expression levels of MMPs and the reduced expression levels of TIMPs were directly associated with the presence of uterine prolapse, indicating that the differential expression levels of MMPs and TIMPs were correlated with the occurrence and development of POP. This data may assist in elucidating the molecular mechanism of MMP and TIMP involvement in POP, and also provide an underlying theoretical basis for the prevention and treatment of POP.
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PMID:Differential expression profiling of matrix metalloproteinases and tissue inhibitors of metalloproteinases in females with or without pelvic organ prolapse. 2511 Jan 12

BACKGROUND Pelvic organ prolapse (POP) is due to age-related atrophy and the weakening of the tissues of the pelvic floor, with degradation of collagen and extracellular matrix (ECM) by metalloproteinases (MMPs). This study aimed to investigates the role of the age-related enzyme klotho, encoded by the KL gene, in cultured fibroblasts obtained from patients with POP and the levels of reactive oxygen species (ROS), interleukin-6 (IL-6), and MMPs. MATERIAL AND METHODS Pelvic floor fibroblasts were obtained from connective tissue from three patients with POP and three normal subjects. Cell proliferation and ROS production were measured using a cell counting kit-8 (CCK-8) assay and flow cytometry. Levels of interleukin-6 (IL-6), klotho, metalloproteinase-1 (MMP-1), MMP-3, extracellular signal-regulated kinases 1/2 (ERK1/2), and p-ERK1/2 were measured by enzyme-linked immunoassay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot. RESULTS In cultured pelvic floor fibroblasts from patients with POP, the expression of klotho protein and klotho mRNA were significantly down-regulated in fibroblasts from patients with POP compared with normal fibroblasts. Klotho supplementation in cultured fibroblasts for patients with POP included increased cell growth, reduced expression of ROS reduction, and reduced the secretion of IL-6. Using qRT-PCR and Western blot, klotho supplementation of fibroblasts from patients with POP increased cell growth and reduced the levels of IL-6 and ROS in a dose-dependent way. CONCLUSIONS Klotho protein reduced the expression of MMP-1 and MMP-3 in fibroblasts from patients with POP by down-regulating the phosphorylation of ERK1/2.
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PMID:Klotho Protein Reduced the Expression of Matrix Metalloproteinase-1 (MMP-1) and Matrix Metalloproteinase-3 (MMP-3) in Fibroblasts from Patients with Pelvic Organ Prolapse (POP) by Down-Regulating the Phosphorylation of ERK1/2. 3111 9