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Dysregulation of protease and protease inhibitors in a mouse model of human pelvic organ prolapse.
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Mice deficient for the fibulin-5 gene (Fbln5(-/-)) develop pelvic organ prolapse (POP) due to compromised elastic fibers and upregulation of matrix metalloprotease (MMP)-9. Here, we used casein zymography, inhibitor profiling, affinity pull-down, and mass spectrometry to discover additional protease
Extracellular matrix proteases contribute to progression of pelvic organ prolapse in mice and humans.
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Pelvic organ prolapse (POP) is a common condition affecting almost half of women over the age of 50. The molecular and cellular mechanisms underlying this condition, however, remain poorly understood. Here we have reported that fibulin-5, an integrin-binding matricellular protein that is essential
Quantification of pelvic organ prolapse in mice: vaginal protease activity precedes increased MOPQ scores in fibulin 5 knockout mice.
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Two mouse models of pelvic organ prolapse have been generated recently, both of which have null mutations in genes involved in elastic fiber synthesis and assembly (fibulin 5 and lysyl oxidase-like 1). Interestingly, although these mice exhibit elastinopathies early in life, pelvic organ prolapse
Transforming growth factor β1 and extracellular matrix protease expression in the uterosacral ligaments of patients with and without pelvic organ prolapse.
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OBJECTIVE
This study was undertaken to evaluate the expression of transforming growth factor β1 (TGF-β1) and matrix metalloproteinase 9 (MMP-9), key regulators of the extracellular matrix composition, in the uterosacral ligaments (USLs) of women with pelvic organ prolapse (POP) compared with
Alteration of elastin metabolism in women with pelvic organ prolapse.
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OBJECTIVE
Although there are many studies about the effects of vaginal birth, the effects of menopause on pelvic floor support have not been identified. We compared elastin metabolism in the uterosacral ligament of women with and without pelvic organ prolapse, and defined the menopausal regulation
Matrix metalloproteinase-9 genetic polymorphisms and the risk for advanced pelvic organ prolapse.
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OBJECTIVE
Matrix metalloproteinase-9 (MMP9) is a protease associated with degradation of collagen and elastin. Because increased MMP9 activity in vaginal tissue has been associated with pelvic organ prolapse (POP), we sought to comprehensively estimate MMP9 genetic variants and the risk for advanced
Protease Inhibition Improves Healing of The Vaginal Wall after Obstetrical Injury: Results from a Preclinical Animal Model.
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Vaginal delivery with obstetrical trauma is a risk factor for pelvic organ prolapse later in life. Loss of fibulin-5 (FBLN5), an elastogenesis-promoting cellular matrix protein, results in prolapse in mice. Here, we evaluated effects of pregnancy, parturition, and obstetrical injury on FBLN5
Regulation of elastolytic proteases in the mouse vagina during pregnancy, parturition, and puerperium.
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Recent evidence indicates that failure of elastic fiber assembly and synthesis is involved in the pathophysiology of pelvic organ prolapse in mice. It has been long been hypothesized that parturition-induced activation of proteases in the vaginal wall and its supportive tissues may contribute to
Alterations in connective tissue metabolism in stress incontinence and prolapse.
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OBJECTIVE
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.
METHODS
We
Elastolytic activity in women with stress urinary incontinence and pelvic organ prolapse.
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OBJECTIVE
Weakening of pelvic supportive tissues is thought to be a contributing etiology in female pelvic floor disorders such as stress urinary incontinence and/or pelvic organ prolapse (SUI/POP). Since elastin modulates the mechanical properties of supportive tissues, we examined elastase
Effect of vaginal distention on elastic fiber synthesis and matrix degradation in the vaginal wall: potential role in the pathogenesis of pelvic organ prolapse.
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Matrix metalloprotease (MMP) activity is increased in the postpartum vagina of wild-type (WT) animals. This degradative activity is also accompanied by a burst in elastic fiber synthesis and assembly. The mechanisms that precipitate these changes are unclear. The goals of this study were to
Effect of Protease Inhibitors in Healing of the Vaginal Wall.
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Impaired elastogenesis and increased degradation of elastic fibers has been implicated in the pathogenesis of pelvic organ prolapse. Loss of the elastogenic organizer, fibulin-5 (FBLN5), leads to pelvic organ prolapse in mice. The objective of this study was to investigate the regulation of FBLN5
The effect of raloxifene, a SERM, on extracellular matrix protein expression of pelvic fibroblasts.
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OBJECTIVE
We hypothesize that the abnormal extracellular matrix (ECM) turnover in pelvic tissues of women with prolapse may be attenuated by raloxifene. We examine the effect of raloxifene on ECM protein expression in pelvic fibroblasts.
METHODS
Pelvic fibroblasts were isolated from cases (N = 6)
MMP9 is protective against lethal inflammatory mass lesions in the mouse colon.
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The family of matrix metalloproteinases (MMPs) is responsible for extracellular matrix degradation during physiological and pathophysiological tissue remodeling processes such as embryogenesis, tissue repair and cancer progression. Despite these important roles of MMPs, inhibition or ablation of
The Potential Beneficial Effects of Resveratrol on Cardiovascular Complications in Marfan Syndrome Patients⁻Insights from Rodent-Based Animal Studies.
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Marfan syndrome (MFS) patients are at risk for cardiovascular disease. In particular, for aortic aneurysm formation, which ultimately can result in a life-threatening aortic dissection or rupture. Over the years, research into a sufficient pharmacological treatment option against aortopathy has
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