ArticleThe Journal of clinical investigation2011
Extracellular matrix proteases contribute to progression of pelvic organ prolapse in mice and humans.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
84 citing papers in PubMed, 4 syntheses or guidelines pooled it, 141 citations in OpenAlex.
- Emerging trends on the mechanism of pelvic organ prolapse from 1997 to 2022: visualization and bibliometric analysis.Frontiers in medicine · 2023Pooled it
- Mouse Knockout Models for Pelvic Organ Prolapse: a Systematic Review.International urogynecology journal · 2022Pooled it
- Aging of Pelvic Floor in Animal Models: A Sistematic Review of Literature on the Role of the Extracellular Matrix in the Development of Pelvic Floor Prolapse.Frontiers in medicine · 2022Pooled it
- Expression changes in pelvic organ prolapse: a systematic review and in silico study.Scientific reports · 2017Pooled it
- Raman spectroscopy for nondestructive detection of vaginal tissue alterations in the fibulin-5 murine model of pelvic organ prolapse.Biophotonics discovery · 2026Article
- Development of a Tissue-Based Extracellular Matrix Vulnerability Score (ECM-V) for Women Undergoing Primary Pelvic Organ Prolapse Surgery.Biomedicines · 2026Article
- Integrin-Binding Matricellular Protein Fibulin-5 Maintains Epidermal Stem Cell Heterogeneity During Skin Aging.Aging cell · 2026Article
- Chapter 4.5: New Proposed Treatments for Pelvic Organ Prolapse.International urogynecology journal · 2026Review
- Fascicular Elastin Impacts Tendon-Specific Ramp-to-Failure and Fatigue Mechanics.Journal of biomechanical engineering · 2025Article
- IGF-1 regulates LARP6-mediated collagen metabolism in vaginal fibroblasts of POP patients via the PI3K/AKT pathway.Scientific reports · 2025Article
- The matricellular protein Fibulin-5 regulates β-cell proliferation in an autocrine/paracrine manner.iScience · 2025Article
- Unveiling the depths of pelvic organ prolapse: From risk factors to therapeutic methods (Review).Experimental and therapeutic medicine · 2025Review
- Unveiling pathogenesis of pelvic organ prolapse through transcriptomic and bioinformatic analyses in uterosacral ligament tissues of postmenopausal women.Frontiers in genetics · 2025Article
- Genetics of Female Pelvic Organ Prolapse: Up to Date.Biomolecules · 2024Review
- Collagen organization and structure inBiomedical optics express · 2024Article
- An Improved Understanding of the Pathophysiology of Pelvic Organ Prolapse: A 3D In Vitro Model under Static and Mechanical Loading Conditions.Advanced healthcare materials · 2024Article
- Collagen organization and structure inbioRxiv : the preprint server for biology · 2024Article
- Women with pelvic organ prolapse and fibulin-5 rs12589592 polymorphism.Revista da Associacao Medica Brasileira (1992) · 2024Article
- Roles and mechanisms of biomechanical-biochemical coupling in pelvic organ prolapse.Frontiers in medicine · 2024Review
- Exosomes derived from mesenchymal stromal cells: a promising treatment for pelvic floor dysfunction.Human cell · 2023Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
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 for elastic fiber assembly, regulated the activity of MMP-9 to maintain integrity of the vaginal wall and prevented development of POP. In murine vaginal stromal cells, fibulin-5 inhibited the β1 integrin-dependent, fibronectin-mediated upregulation of MMP-9. Mice in which the integrin-binding motif was mutated to an integrin-disrupting motif (Fbln5RGE/RGE) exhibited upregulation of MMP-9 in vaginal tissues. In contrast to fibulin-5 knockouts (Fbln5-/-), Fbln5RGE/RGE mice were able to form intact elastic fibers and did not exhibit POP. However, treatment of mice with β-aminopropionitrile (BAPN), an inhibitor of matrix cross-linking enzymes, induced subclinical POP. Conversely, deletion of Mmp9 in Fbln5-/- mice significantly attenuated POP by increasing elastic fiber density and improving collagen fibrils. Vaginal tissue samples from pre- and postmenopausal women with POP also displayed significantly increased levels of MMP-9. These results suggest that POP is an acquired disorder of extracellular matrix and that therapies targeting matrix proteases may be successful for preventing or ameliorating POP in women.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.