elastin and Urinary-Incontinence--Stress

The Integral Theory (IT) states that urinary stress and urge symptoms mainly arise from lax suspensory ligaments, which are a consequence of altered collagen/elastin. Four important muscle groups (pubococcygeal muscle, levatorplate, longitudinal muscle of the anus, and the puborectalis muscle) are only able to guarantee the opening and closure mechanism of the bladder, the urethra and the anal tube if the suspensory ligaments are intact. The first practical application of the IT was the repair of the pubourethral ligament (PUL) known as tension-free vaginal tape (TVT).. What is the practical impact of the IT today? Do lax suspensory ligaments play a role in stress and urge urinary incontinence, fecal incontinence, voiding difficulties, and pelvic pain?. Evaluation of the literature, data, and experiences concerning IT.. The pathophysiology of pelvic floor disorders has been widely proven and surgical concepts were developed to reconstruct the ligaments with the result of regaining function. Suburethral tapes are accepted as the standard of care for urinary stress incontinence. In addition, the correction of cervical ring defects, the lateral and central cystoceles, the uterosacral ligaments, the perineal body, and the rectovaginal fascia were adapted and newly developed with the aim of alleviating symptoms. Newly published data prove the cure of symptoms in a high percentage of cases. The complex conditions and function of the pelvic floor can be understood much better by using the diagnostic algorithm and with knowledge of the basic pathophysiology.. The basic IT message: repair the structure (ligaments) and you will restore the function is true for all pelvic floor ligaments.

Topics: Anal Canal; Collagen; Elastin; Fecal Incontinence; Female; Humans; Ligaments; Male; Pelvic Pain; Suburethral Slings; Urethra; Urinary Bladder; Urinary Incontinence, Stress; Urinary Incontinence, Urge; Urodynamics

To review the scientific and clinical literature to assess the basis for the use of biomaterials in stress urinary incontinence (SUI) and pelvic organ prolapse (POP). Pelvic floor diseases (PFDS), such as SUI and POP, are common and vexing disorders. While synthetic mesh-based repairs have long been considered an option for PFD treatment, and their efficacy established in randomised clinical trials, safety of its use has recently been called into question.. Using the PubMed, MEDLINE and Medical Subject Headings (MeSH) databases, we performed a critical review of English-language publications that contained the following keywords: 'pelvic organ prolapse', 'stress urinary incontinence', 'mesh', 'biomaterial', 'collagen', 'elastin' and 'extracellular matrix'. After reviewing for relevance for mesh use in the pelvis by two independent reviewers with a third available in the case of disagreement, a total of 60 articles were included in the present review.. We found that many of the potential causes of PFDs are due to altered metabolism of patient extracellular matrix (specifically collagen, elastin, and their respective enzymes) and as such, repairs using native tissue may suffer from the same abnormalities leading to a subsequent lack of repair integrity. However, mesh use is not without its unique risks. Several publications have suggested that biomaterials may undergo alteration after implantation, but these findings have not been demonstrated in the normal milieu.. While the decision for the use of synthetic mesh is scientifically sound, its benefits and risks must be discussed with the patient in an informed decision-making process.

Topics: Biocompatible Materials; Collagen; Elastin; Female; Humans; Pelvic Organ Prolapse; Randomized Controlled Trials as Topic; Surgical Mesh; Urinary Incontinence, Stress

Pelvic floor disorders (PFDs) such as stress urinary incontinence (SUI) and pelvic organ prolapse (POP) may share a common pathophysiological process related to pelvic floor tissue laxity and loss of support. We reviewed recent literature on observed biochemical changes in women with SUI and POP, linking them to genetic predisposition. We found that studies of pelvic tissues showed differences between control subjects and women with POP and SUI in collagen and elastin structure at a molecular and fibrillar level. Studies were heterogeneous but showed a trend towards decreased collagen and elastin content. The contribution of matrix metalloproteinases to increased collagenolysis can be related to genetic polymorphisms present in higher frequency in women with PFD. Extracellular matrix (ECM) protein turnover plays a role in the development of POP and SUI, but much remains to be understood of this complex dynamic interplay of enzymes, proteins and molecules. Genotyping of candidate genes participating in ECM formation will elucidate the missing link between the manifestation of the disease and the biochemical changes observed systematically, in addition to those in the pelvic floor.

Topics: Collagen; Elastin; Extracellular Matrix; Female; Genetic Predisposition to Disease; Humans; Matrix Metalloproteinases; Pelvic Floor; Pelvic Organ Prolapse; Risk Factors; Urinary Incontinence, Stress

We describe current knowledge about collagen/elastin and extracellular matrix metabolism in the genitourinary tract with special emphasis on stress urinary incontinence. We also explored the influence of genetics and reproductive hormones on extracellular matrix metabolism.. We performed a MEDLINE® search from 1995 to February 2011 using the key words stress urinary incontinence, pelvic organ prolapse, extracellular matrix, collagen, elastin, matrix metalloproteinase, collagenase, tissue inhibitors of matrix metalloproteinase, elastin metabolism, elastase, connective tissue, supportive tissue, mechanical stress, biomechanical properties, selective estrogen receptor modulators, transforming growth factor-β and wound healing.. The literature searched produced data on 4 areas of significance for extracellular matrix metabolism in patients with stress urinary incontinence and prolapse, including collagen, elastin and transforming growth factor-β. Data on collagen metabolism continue to support the hypothesis of increased turnover involving matrix metalloproteinases and serine proteases in pelvic tissues of affected individuals. Elastin metabolism studies suggest increased degradation but also abnormal elastin fiber synthesis. Epidemiological data indicate a genetic predisposition to abnormal extracellular matrix in affected individuals while human tissue and animal models reveal differential expression of candidate genes involved in structural proteins. Transforming growth factor-β pathways have been documented to be involved in stress urinary incontinence in human tissues and animal models. Finally, these extracellular matrix metabolisms are modulated by reproductive hormones and selective estrogen receptor modulators.. Pelvic tissue from women with stress urinary incontinence and pelvic organ prolapse show a genetic predisposition to abnormal extracellular matrix remodeling, which is modulated by reproductive hormones, trauma, mechanical stress load and aging. This progressive remodeling contributes to stress urinary incontinence/pelvic organ prolapse by altering normal tissue architecture and mechanical properties.

Topics: Animals; Collagen; Connective Tissue; Cystocele; Elastin; Estrogens; Extracellular Matrix; Humans; Matrix Metalloproteinase 2; Stress, Mechanical; Transforming Growth Factor beta; Urinary Incontinence, Stress

Stress urinary incontinence (SUI) is more prevalent among women who deliver vaginally than women who have had a cesarean section, suggesting that tissue repair after vaginal delivery is insufficient. A single dose of mesenchymal stem cells (MSCs) has been shown to partially restore urethral function in a model of SUI. The aim of the present study was to determine if increasing the number of doses of MSCs improves urethral and pudendal nerve function and anatomy. We hypothesized that increasing the number of MSC doses would accelerate recovery from SUI compared with vehicle treatment. Rats underwent pudendal nerve crush and vaginal distension or a sham injury and were treated intravenously with vehicle or one, two, or three doses of 2 × 10

Topics: Animals; Bone Marrow Transplantation; Connective Tissue; Elastin; Female; Mesenchymal Stem Cell Transplantation; Nerve Crush; Neuromuscular Diseases; Postpartum Period; Pudendal Nerve; Rats; Rats, Sprague-Dawley; Stem Cell Transplantation; Urethra; Urinary Incontinence, Stress; Vagina

Polypropylene meshes cause severe complications in some patients. Materials that are biomechanically compatible and can better integrate into host tissues are urgently needed.. To design an oestradiol-releasing electrospun poly-l-lactic acid (PLA) mesh and evaluate its ability to stimulate new extracellular matrix and new blood vessel formation.. Human adipose derived mesenchymal cells (ADMSC) were isolated from fat. PLA meshes with micro- to nano-sized fibres containing 1%, 5%, and 10% oestradiol were constructed and used for in vitro and in vivo experiments.. The angiogenic potential of the fibrous meshes was evaluated using an in vivo chorioallantoic membrane and an in vitro chick aortic arch assays.. Oestradiol release was measured fluorometrically. The effect of fibrous meshes on proliferation and extracellular matrix (ECM) production of ADMSC was assessed using immunohistology. Mechanical properties were tested using a tensiometer.. The ultrastructure of the mesh was not affected by the inclusion of oestradiol and mechanical properties were only slightly modified. Oestradiol was released from PLA meshes over a 5-mo period. ADMSCs cultured on oestradiol-releasing PLA meshes produced more ECM involving collagen I, collagen III, and elastin. Oestradiol-releasing meshes doubled new blood vessel formation in the chorioallantoic membrane assay (p=0.001) and outgrowth of pro-angiogenic cells in the aortic arch assay (p=0.001). Further studies in longer-term animal models are required to confirm these results.. Oestradiol-releasing PLA meshes increase ECM production and stimulate angiogenesis. As such, they are promising candidate materials to be used in pelvic floor repair and to improve the initial healing phase of a repair material following implantation.. In this study, we designed a tissue engineered material to be used to support weakened pelvic floor tissues in women to avoid the complications associated with current surgical mesh. Our results showed that this material can stimulate new blood vessel formation in simple chick assays and tissue production in vitro. Both properties should help with the integration of this material into patients' tissues and merit further study in physiologically relevant animal models.

Topics: Biocompatible Materials; Chorioallantoic Membrane; Collagen; Elastin; Estradiol; Extracellular Matrix; Female; Humans; Microscopy, Electron, Scanning; Neovascularization, Physiologic; Pelvic Floor; Pelvic Organ Prolapse; Polypropylenes; Surgical Mesh; Tissue Engineering; Treatment Outcome; Urinary Incontinence, Stress

This study investigated whether microRNA-214 (miR-214) targets mitofusin-2 (Mfn2) in the process of fibroblast differentiation of adipose-derived mesenchymal stem cells (ADMSCs) during pelvic floor dysfunction (PFD) in Sprague Dawley (SD) rats with birth trauma.. The ADMSCs were isolated from 4-6 week male SD rats (n = 20) and were cultured and divided into the blank, miR-214 mimic negative control (NC), miR-214 mimic, miR-214 inhibitor NC, miR-214 inhibitor, empty vector, Mfn2 over-expression and miR-214 + Mfn2 over-expression groups. Fibroblast differentiation of ADMSCs was measured with immunocytochemistry and immunofluorescence methods. The expression of miR-214 and the mRNA and protein expression of Mfn2, FSP1, Collagen I, Collagen III, Elastin, LOX, Fibulin-5, PPAR-γ and Runx2 were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. A dual-luciferase reporter assay was performed to confirm whether Mfn2 was the target gene of miR-214.. During ADMSC differentiation into fibroblasts, miR-214 expression was up-regulated, but the expression of Mfn2 was down-regulated. Fibroblast differentiation of ADMSCs was promoted in the miR-214 mimic group but was inhibited in the miR-214 inhibitor and Mfn2 over-expression groups. The expression of Mfn2 was decreased, but the expression of FSP1, Collagen I, Collagen III, Elastin, LOX, Fibulin-5, PPAR-γ or Runx2 was increased in the miR-214 mimic group; the miR-214 inhibitor group and Mfn2 over-expression group exhibited the opposite results. Mfn2 was the target gene of miR-214.. The study provided strong evidence that miR-214 could promote fibroblast differentiation of ADMSCs by down-regulating Mfn2 to improve PFD in SD rats with birth trauma.

Topics: Adipogenesis; Adipose Tissue; Animals; Antagomirs; Calcium-Binding Proteins; Cell Differentiation; Cells, Cultured; Collagen Type I; Collagen Type III; Elastin; Female; GTP Phosphohydrolases; Male; Membrane Proteins; Mesenchymal Stem Cells; MicroRNAs; Mitochondrial Proteins; Osteogenesis; Pelvic Floor; Rats; Rats, Sprague-Dawley; Urinary Incontinence, Stress

To study the expression of hormonal receptors, collagen, elastin, proteoglycans, and VIP in the vaginal wall of women with stress urinary incontinence (SUI).. Fifty-eight specimens of the anterior vaginal wall (28 women with SUI) were processed by Ventana immunostaining method.. Both groups were compatible for age, BMI, and obstetric history. Positive ER-α and ER-β immunoreaction was observed in 46.4% and 3.6% of SUI (43.3% and 33.3% of controls) (p < 0.05), respectively, and PR immunoreaction in 39.3% of SUI (46.7% of controls). Collagen I and III immunoreaction was observed in 28,6% and 21.4% of SUI (30.% and 36.7% of controls), respectively, and elastin, decorin, and fibromodulin immunoreaction in 10.7%, 10.7%, and 10.7% of SUI (50%, 33.3%, 33,.3% of controls) (p < 0.05), respectively. VIP immunoreaction was observed in 7.1% of SUI (36.7% of controls).. Imunoexpression of ER-P, elastin, decorin, fibromodulin, and VIP was significantly lower in SUI than controls, showing that the ER-β dependent re-modeling of the extracellular matrix of vaginal tissues is the main mechanism of SUI.

Topics: Aged; Case-Control Studies; Collagen; Collagen Type I; Collagen Type III; Decorin; Elastin; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Fibromodulin; Humans; Immunohistochemistry; Middle Aged; Proteoglycans; Receptors, Progesterone; Urinary Incontinence, Stress; Vagina; Vasoactive Intestinal Peptide

The present study provides evidence that a pure population of human smooth muscle progenitor cells (pSMCs) derived from human pluripotent stem cells (hPSCs) (human embryonic stem cells and patient induced pluripotent stem cells) restores urethral sphincter function by two mechanisms: modulation of extracellular matrix protein metabolism in vivo and pSMC proliferation and differentiation into smooth muscle cells to regenerate the muscle layer in the lower urinary tract. These findings on the in vivo effects of human pSMCs should aid in optimizing regenerative therapies using human myoblasts.

Topics: Animals; Blotting, Western; Cell Survival; Cell Tracking; Collagen Type III; Elastin; Extracellular Matrix; Female; Humans; Luminescent Measurements; Mice, SCID; Myocytes, Smooth Muscle; Pluripotent Stem Cells; Rats, Nude; Stem Cells; Urethra; Urinary Incontinence, Stress

Synthetic non-absorbable meshes are widely used to augment surgical repair of stress urinary incontinence (SUI) and pelvic organ prolapse (POP); however, there is growing concern such meshes are associated with serious complications. This study compares the potential of two autologous cell sources for attachment and extra-cellular matrix (ECM) production on a biodegradable scaffold to develop tissue engineered repair material (TERM).. Human oral fibroblasts (OF) and human adipose-derived stem cells (ADSC) were isolated and cultured on thermo-annealed poly-L-lactic acid (PLA) scaffolds for two weeks under either unrestrained conditions or restrained (either with or without intermittent stress) conditions. Samples were tested for cell metabolic activity (AlamarBlue® assay), contraction (serial photographs analyzed with image J software), total collagen production (Sirius red assay), and production of ECM components (immunostaining for collagen I, III, and elastin; and scanning electron microscopy) and biomechanical properties (BOSE tensiometer). Differences were statistically tested using two sample t-test.. Both cells showed good attachment and proliferation on scaffolds. Unrestrained scaffolds with ADSC produced more total collagen and a denser homogenous ECM than OF under same conditions. Restrained conditions (both with and without intermittent stress) gave similar total collagen production, but improved elastin production for both cells, particularly OF. The addition of any cell onto scaffolds led to an increase in biomechanical properties of scaffolds compared to unseeded scaffolds.. OF and ADSC both appear to be suitable cell types to combine with biodegradable scaffolds, in the development of a TERM for the treatment of SUI and POP. Neurourol. Urodynam. 33:531-537, 2014. © 2013 Wiley Periodicals, Inc.

Topics: Absorbable Implants; Cell Proliferation; Collagen Type I; Collagen Type II; Collagen Type III; Elastin; Extracellular Matrix; Fibroblasts; Humans; Lactic Acid; Microscopy, Electron, Scanning; Mouth; Pelvic Organ Prolapse; Polyesters; Polymers; Stem Cells; Subcutaneous Fat; Tissue Engineering; Tissue Scaffolds; Urinary Incontinence, Stress

Topics: Animals; Collagen; Connective Tissue; Cystocele; Elastin; Extracellular Matrix; Humans; Transforming Growth Factor beta; Urinary Incontinence, Stress

To investigate the effects of birth trauma and estrogen on urethral elastic fibers and elastin expression.. Pregnant rats were subjected to sham operation (Delivery-only), DVDO (delivery, vaginal distension and ovariectomy), or DVDO + E₂ (estrogen). At 2, 4, 8, or 12 weeks, their urethras were harvested for elastic fiber staining and reverse transcription-polymerase chain reaction analysis. Urethral cells were treated with transforming growth factor- β1 (TGFβ1) and/or estrogen and analyzed for elastin mRNA expression. Urethral cells were also examined for the activities of Smad1- and Smad3/4-responsive elements in response to TGFβ1 and estrogen.. At 8 weeks post-treatment, the urethras of DVDO rats had fewer and shorter elastic fibers when compared with Delivery-only rats, and those of DVDO + E₂ rats had fewer and shorter elastic fibers when compared with DVDO rats. Elastin mRNA was expressed at low levels in Delivery-only rats and at increasingly higher levels in DVDO rats at 2, 4, and 8 weeks but at sharply lower levels in DVDO + E₂ rats when compared with DVDO rats at 8 weeks. Urethral cells expressed increasingly higher levels of elastin mRNA in response to increasing concentrations of TGFβ1 up to 1 ng/mL. At this TGFβ1 concentration, urethral cells expressed significantly lower levels of elastin mRNA when treated with estrogen before or after TGFβ1 treatment. Both Smad1- and Smad3/4-responsive elements were activated by TGFβ1 and such activation was suppressed by estrogen.. Birth trauma appears to activate urethral elastin expression via TGFβ1 signaling. Estrogen interferes with this signaling, resulting in improper assembly of elastic fibers.

Topics: Animals; Cells, Cultured; Drug Implants; Elastic Tissue; Elastin; Epithelial Cells; Estradiol; Female; Gene Expression Regulation; Ovariectomy; Parturition; Pregnancy; Random Allocation; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Smad Proteins; Stress, Mechanical; Transforming Growth Factor beta1; Urethra; Urinary Incontinence, Stress

Altered elastin metabolism is implicated in pelvic floor disorders. We studied neutrophil elastase (NE) and matrix metalloproteinase (MMP) activities in vaginal tissues from premenopausal women with stress urinary incontinence (SUI).. Elastase and NE activities in vaginal tissues were assessed. Protein and mRNA expressions were determined by RT-PCR and Western blot. Total elastin and collagen contents were evaluated. To compare the relative elastolytic effect of NE and MMP-2, we used their respective antibodies to immunoprecipitate these proteins from vaginal fibroblast extracts prior to assessing elastase activity.. Elastase activity in vaginal wall tissues was significantly higher in the secretory compared to the proliferative phase. NE mRNA and protein expressions were similar between control and SUI tissues from the secretory phase. However, NE activity in the SUI tissues was higher compared to control tissues. The mRNA expression of alpha-1 antitrypsin (ATT) was higher in control tissues from the proliferative phase compared to those from the secretory phase, while no difference was observed in SUI tissues between either phase. Protein expression of the active form of ATT was decreased in SUI tissues compared to controls during the secretory phase. Anti-NE antibody reduced total elastase activity by 60-70%, compared to less than 20% reduction with anti-MMP-2 antibody.. During the secretory phase, elastolytic activity is increased in pelvic tissues from women with SUI, through an increase in NE activity and a concurrent decrease in ATT expression. The serine protease, NE, appears to be a more significant modulator of elastase activity compared to MMP-2.

Topics: Adult; alpha 1-Antitrypsin; Blotting, Western; Collagen; Elastin; Female; Fluorescent Antibody Technique; Humans; Leukocyte Elastase; Matrix Metalloproteinases; Middle Aged; Oligonucleotide Array Sequence Analysis; Relaxin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Urinary Incontinence, Stress; Vagina

To investigate changes in mRNA and protein levels of biglycan (BGN), decorin (DCN) and fibromodulin (FMOD) in vaginal wall tissue from women with stress urinary incontinence (SUI) compared to menstrual-cycle matched continent women.. We determined mRNA expressions of BGN, DCN and FMOD by quantitative real-time PCR. They were localized in vaginal wall tissue by immunohistochemistry. We performed western blot analysis to examine protein expression.. BGN, DCN and FMOD co-localized with collagen and elastin in the extracellular matrix (ECM) of vaginal wall tissue from both groups. The mRNA expression of FMOD was significantly lower in cases versus controls in the proliferative phase (P = 0.03). DCN mRNA expression in cases was higher in the proliferative (P = 0.05) and secretory phases (P = 0.02) versus controls. BGN mRNA expression showed no significant differences in either phase. Protein expression of FMOD in cases was lower in the proliferative phase versus controls (six out of nine pairs), whereas DCN and BGN protein expression in the secretory phase in cases was higher (seven out of nine pairs).. BGN, DCN and FMOD expressions in vaginal wall tissue differ in women with SUI and are hormonally modulated. Differences in small proteoglycans may contribute to the altered pelvic floor connective tissues found in these women.

Topics: Adult; Biglycan; Collagen Type I; Decorin; Elastin; Extracellular Matrix Proteins; Female; Fibromodulin; Humans; Immunohistochemistry; Menstrual Cycle; Middle Aged; Proteoglycans; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Urinary Incontinence, Stress; Vagina

To evaluate differential expression of transforming growth factor (TGF-beta1), latent transforming factor-binding proteins (LTBP-1, LTBP-2) and elastin microfibril components (fibrillin-1 and fibrillin-2) in vaginal tissue from women with stress urinary incontinence (SUI).. In this case-control study, vaginal tissue from women in both phases of the menstrual cycle was obtained. Messenger RNA (mRNA) expressions of LTBP-1, LTBP-2, fibrillin-1, fibrillin-2 and TGF-beta1 were determined by relative real-time quantification PCR. Tissue localization was analysed by immunohistochemistry, and semiquantitative protein expression was evaluated by Western blot analysis.. Vaginal wall fibroblasts synthesized all proteins tested. LTBP-1, LTBP-2 and TGF-beta1 co-localized with elastin microfibrils, fibrillin-1 and fibrillin-2 in the extracellular matrix. LTBP-1 mRNA and protein expressions were higher in control versus women affected with SUI in the proliferative phase (P = 0.04), while in the secretory phase, mRNA expression in cases was higher (P = 0.04). Fibrillin-1 mRNA was higher in women affected by SUI versus controls in both phases, but no statistical differences in fibrillin-1 protein expression were observed between the two groups in either phase. LTBP-2 and TGF-beta1 mRNA expressions showed the same trends as LTBP-1.. LTBP-1, LTBP-2, TGF-beta1, fibrillin-1, and fibrillin-2 expressions are hormonally regulated in vaginal wall fibroblasts and differ in women affected by SUI when compared to controls. These data suggest a mechanism to regulate TGF-beta1 activity in pelvic connective tissue.

Topics: Case-Control Studies; Connective Tissue; Elastin; Extracellular Matrix Proteins; Female; Fibrillin-1; Fibrillin-2; Fibrillins; Fibroblasts; Gonadal Hormones; Humans; Intracellular Signaling Peptides and Proteins; Latent TGF-beta Binding Proteins; Microfibrils; Microfilament Proteins; Pelvis; RNA, Messenger; Transforming Growth Factor beta; Transforming Growth Factor beta1; Urinary Incontinence, Stress; Vagina

Changes in structural support of the urethra and bladder neck have been proposed as important factors in the pathogenesis of stress urinary incontinence (SUI). In this context, we undertook an ultrastructural study on the periurethral connective tissue with an emphasis on incontinent women with normotonic and hypotonic urethras. Small specimens of periurethral connective tissue were obtained by dissection during a tension-free vaginal tape-implantation procedure in 34 stress urinary incontinent postmenopausal women with a normotonic urethra and 9 stress urinary incontinent postmenopausal women with a hypotonic urethra. In the samples taken from stress-incontinent women with a normotonic urethra, intact elastic fibers were closely connected with collagen fibers, smooth muscle cells and fibrocytes. In the samples taken from stress-incontinent women with a hypotonic urethra, we detected irregular fragmented distribution of the elastin within the tissue. We assume that these structural changes lead to functional consequences, such as diminished tissue extensibility and loss of stability surrounding the female urethra. These altered connective tissue properties may affect the mechanism of urethral closure under stress (e.g., coughing) and therefore contribute to the occurrence of SUI with a hypotonic urethra.

Topics: Aged; Elastin; Extracellular Matrix; Female; Humans; Middle Aged; Postmenopause; Urethra; Urinary Incontinence, Stress

The purpose of this study was to investigate the effect of relaxin on extracellular matrix protein expression in pelvic fibroblasts that were cultured from women with stress urinary incontinence compared with asymptomatic control subjects.. Periurethral vaginal wall fibroblasts from premenopausal women with stress urinary incontinence and continent women (in both the proliferative and secretory phase of the menstrual cycle) were stimulated with increasing concentrations of relaxin (0-500 ng/mL). The supernatant was sampled for matrix metalloproteinase-2 and -9 by zymography. Tissue inhibitors of metalloproteinase-1 and -2 and alpha-1 antitrypsin were evaluated with Western blot. Total elastase activity was measured by generation of free amino groups from succinylated elastin. Increasing concentrations of alpha-1 antitrypsin were added to cell lysate to evaluate total elastase activity inhibition.. Proliferative-phase stress urinary incontinence fibroblasts demonstrated an increase in matrix metalloproteinase-2 and no change in matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-1 and -2 expressions with increasing relaxin concentrations. Cells from control subjects showed increased expression of matrix metalloproteinase-2 and -9, but no change in tissue inhibitors of metalloproteinases. Secretory-phase stress urinary incontinence fibroblasts showed no response in matrix metalloproteinase or tissue inhibitors of metalloproteinase expressions with relaxin stimulation. Secretory-phase control fibroblasts reacted by increasing matrix metalloproteinase-2 and -9 and tissue inhibitors of metalloproteinase-2. With respect to total elastase activity and alpha-1 antitrypsin expression, increasing doses of relaxin appear to increase elastolytic activity in stress urinary incontinence cells by decreasing the expression of alpha-1 antitrypsin in proliferative phase cells or increasing the total elastase activity in secretory phase cells. Fibroblast total elastase activity was inhibited by increasing concentrations of alpha-1 antitrypsin.. Elastase activity appears to be increased in relaxin-stimulated stress urinary incontinence fibroblasts by either decreased inhibitor (alpha-1 antitrypsin) production or increased elastase activity.

Topics: Adult; alpha 1-Antitrypsin; Case-Control Studies; Cells, Cultured; Dose-Response Relationship, Drug; Elastin; Female; Fibroblasts; Follicular Phase; Humans; Leukocyte Elastase; Luteal Phase; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Middle Aged; Relaxin; Tissue Inhibitor of Metalloproteinase-2; Urinary Incontinence, Stress; Vagina