Effect of Protease Inhibitors in Healing of the Vaginal Wall
Open Access
- 26 August 2019
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 9 (1), 1-10
- https://doi.org/10.1038/s41598-019-48527-0
Abstract
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 after surgical injury of the vaginal wall using the rat as a preclinical animal model. Both endogenous and recombinant FBLN5 were degraded after surgical injury. Estrogen did not alter the dramatic loss of vaginal FBLN5 in the acute phase after injury (12–48 h), but resulted in rescue of the poor recovery of FBLN5 levels in the late phase (7 d) of healing in ovariectomized animals. In contrast with estrogen, the general MMP inhibitor, actinonin, abrogated injury-induced degradation of FBLN5 significantly. Further, actinonin rescued the negative effects of injury on biomechanics, histomorphology, and elastic fibers. Control of excessive matrix degradation by local application of actinonin at the time of surgery may lead to improved elastic fiber regeneration and wound healing, thereby potentially enhancing pelvic floor recovery after reconstructive surgery for prolapse.Funding Information
- U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (AG028048)
This publication has 44 references indexed in Scilit:
- Pelvic Organ Prolapse in Fibulin-5 Knockout Mice: Pregnancy-Induced Changes in Elastic Fiber Homeostasis in Mouse VaginaThe American Journal of Pathology, 2007
- Failure of Elastic Fiber Homeostasis Leads to Pelvic Floor DisordersThe American Journal of Pathology, 2006
- The hidden epidemic of pelvic floor dysfunction: Achievable goals for improved prevention and treatmentAmerican Journal of Obstetrics and Gynecology, 2005
- Matrix metalloproteinases in cancer: comparison of known and novel aspects of their inhibition as a therapeutic approachExpert Review of Anticancer Therapy, 2005
- Fibulin-5 promotes wound healing in vivo1Journal of the American College of Surgeons, 2004
- Epidemiologic evaluation of reoperation for surgically treated pelvic organ prolapse and urinary incontinenceAmerican Journal of Obstetrics and Gynecology, 2003
- Upregulation of matrix metalloproteinases in a model of T cell mediated tissue injury in the gut: analysis by gene array and in situ hybridisationGut, 2002
- Fibulin-5/DANCE is essential for elastogenesis in vivoNature, 2002
- Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivoNature, 2002
- Characterization of Matrix Metalloproteinases Produced by Rat Alveolar MacrophagesAmerican Journal of Respiratory Cell and Molecular Biology, 1999