Protease Inhibition Improves Healing of The Vaginal Wall after Obstetrical Injury: Results from a Preclinical Animal Model
Autor: | Jennifer J. Hamner, Jesus F. Acevedo, Haolin Shi, R. Ann Word, Maria E. Florian-Rodriguez |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Physiology medicine.medical_treatment Obstetric Surgical Procedures Urology lcsh:Medicine Matrix metalloproteinase Hydroxamic Acids Article Pelvic Organ Prolapse Extracellular matrix 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Pregnancy Risk Factors Uterine Prolapse medicine Animals Humans Protease Inhibitors Risk factor Actinonin lcsh:Science Extracellular Matrix Proteins Wound Healing 030219 obstetrics & reproductive medicine Multidisciplinary Protease business.industry Vaginal delivery lcsh:R Translational research Delivery Obstetric medicine.disease Recombinant Proteins Rats Pregnancy Complications 030104 developmental biology chemistry Vagina Female lcsh:Q business |
Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-11 (2020) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | 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 content, elastic fibers, biomechanics, and histomorphology of the vaginal wall in rats. Further, we analyzed the effects of actinonin, a protease inhibitor, on obstetrical injury of the vaginal wall. Vaginal FBLN5 decreased significantly in pregnancy, and injury resulted in further downregulation. Stiffness of the vaginal wall decreased 82% in pregnant rats and 74% (p = 0.019) with injury relative to uninjured vaginal delivery controls at 3d. Actinonin ameliorated loss of FBLN5, rescued injury-induced loss of elastic fibers and biomechanical properties after parturition, and reduced the area of injury 10-fold. We conclude that pregnancy and parturition have a profound impact on vaginal FBLN5 and biomechanics of the vaginal wall. Further, obstetrical injury has significant deleterious impact on recovery of the vaginal wall from pregnancy. Actinonin, a non-specific matrix metalloprotease inhibitor, improved recovery of the parturient vaginal wall after obstetrical injury. |
Databáze: | OpenAIRE |
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