Dataset Information

Dysregulation of protease and protease inhibitors in a mouse model of human pelvic organ prolapse.

ABSTRACT: 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 upregulated in the vaginal wall of Fbln5(-/-) mice, herein named V1 (25 kDa). V1 was a serine protease with trypsin-like activity similar to protease, serine (PRSS) 3, a major extrapancreatic trypsinogen, was optimum at pH 8.0, and predominantly detected in estrogenized vaginal epithelium of Fbln5(-/-) mice. PRSS3 was (a) localized in epithelial secretions, (b) detected in media of vaginal organ culture from both Fbln5(-/-) and wild type mice, and (c) cleaved fibulin-5 in vitro. Expression of two serine protease inhibitors [Serpina1a (?1-antitrypsin) and Elafin] was dysregulated in Fbln5(-/-) epithelium. Finally, we confirmed that PRSS3 was expressed in human vaginal epithelium and that SERPINA1 and Elafin were downregulated in vaginal tissues from women with POP. These data collectively suggest that the balance between proteases and their inhibitors contributes to support of the pelvic organs in humans and mice.

SUBMITTER: Budatha M

PROVIDER: S-EPMC3577807 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Dysregulation of protease and protease inhibitors in a mouse model of human pelvic organ prolapse.

Budatha Madhusudhan M Silva Simone S Montoya Teodoro Ignacio TI Suzuki Ayako A Shah-Simpson Sheena S Wieslander Cecilia Karin CK Yanagisawa Masashi M Word Ruth Ann RA Yanagisawa Hiromi H

PloS one 20130220 2

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 upregulated in the vaginal wall of Fbln5(-/-) mice, herein named V1 (25 kDa). V1 was a serine protease with trypsin-like activity similar to protease, serine (PRSS) 3, a major extrapancreatic trypsin ...[more]

PMID: 23437119

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Project description:ObjectivesTo describe pelvic organ prolapse surgical success rates using a variety of definitions with differing requirements for anatomic, symptomatic, or re-treatment outcomes.MethodsEighteen different surgical success definitions were evaluated in participants who underwent abdominal sacrocolpopexy within the Colpopexy and Urinary Reduction Efforts trial. The participants' assessments of overall improvement and rating of treatment success were compared between surgical success and failure for each of the definitions studied. The Wilcoxon rank sum test was used to identify significant differences in outcomes between success and failure.ResultsTreatment success varied widely depending on definition used (19.2-97.2%). Approximately 71% of the participants considered their surgery "very successful," and 85.2% considered themselves "much better" than before surgery. Definitions of success requiring all anatomic support to be proximal to the hymen had the lowest treatment success (19.2-57.6%). Approximately 94% achieved surgical success when it was defined as the absence of prolapse beyond the hymen. Subjective cure (absence of bulge symptoms) occurred in 92.1% while absence of re-treatment occurred in 97.2% of participants. Subjective cure was associated with significant improvements in the patient's assessment of both treatment success and overall improvement, more so than any other definition considered (P<.001 and <.001, respectively). Similarly, the greatest difference in symptom burden and health-related quality of life as measured by the Pelvic Organ Prolapse Distress Inventory and Pelvic Organ Prolapse Impact Questionnaire scores between treatment successes and failures was noted when success was defined as subjective cure (P<.001).ConclusionThe definition of success substantially affects treatment success rates after pelvic organ prolapse surgery. The absence of vaginal bulge symptoms postoperatively has a significant relationship with a patient's assessment of overall improvement, while anatomic success alone does not.Level of evidenceII.

Dataset Information

Dysregulation of protease and protease inhibitors in a mouse model of human pelvic organ prolapse.

Publications

Dysregulation of protease and protease inhibitors in a mouse model of human pelvic organ prolapse.

Similar Datasets

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