Effect of Protease Inhibitors in Healing of the Vaginal Wall

Maria Florian-Rodriguez, Kathleen Chin, Jennifer Hamner, Jesus Acevedo, Patrick Keller, R. Ann Word

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number12354
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

Protease Inhibitors
Elastic Tissue
Pelvic Organ Prolapse
Intraoperative Complications
Reconstructive Surgical Procedures
Wounds and Injuries
Estrogens
Pelvic Floor
Matrix Metalloproteinase Inhibitors
Prolapse
Biomechanical Phenomena
Wound Healing
fibulin
Regeneration
Animal Models
actinonin

ASJC Scopus subject areas

  • General

Cite this

Effect of Protease Inhibitors in Healing of the Vaginal Wall. / Florian-Rodriguez, Maria; Chin, Kathleen; Hamner, Jennifer; Acevedo, Jesus; Keller, Patrick; Word, R. Ann.

In: Scientific Reports, Vol. 9, No. 1, 12354, 01.12.2019.

Research output: Contribution to journalArticle

Florian-Rodriguez, Maria ; Chin, Kathleen ; Hamner, Jennifer ; Acevedo, Jesus ; Keller, Patrick ; Word, R. Ann. / Effect of Protease Inhibitors in Healing of the Vaginal Wall. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
@article{fe735bcb5e2b4eb78e460d627ca96fea,
title = "Effect of Protease Inhibitors in Healing of the Vaginal Wall",
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.",
author = "Maria Florian-Rodriguez and Kathleen Chin and Jennifer Hamner and Jesus Acevedo and Patrick Keller and Word, {R. Ann}",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41598-019-48527-0",
language = "English (US)",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Effect of Protease Inhibitors in Healing of the Vaginal Wall

AU - Florian-Rodriguez, Maria

AU - Chin, Kathleen

AU - Hamner, Jennifer

AU - Acevedo, Jesus

AU - Keller, Patrick

AU - Word, R. Ann

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85071431085&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071431085&partnerID=8YFLogxK

U2 - 10.1038/s41598-019-48527-0

DO - 10.1038/s41598-019-48527-0

M3 - Article

C2 - 31451729

AN - SCOPUS:85071431085

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 12354

ER -