Effect of Protease Inhibitors in Healing of the Vaginal Wall

Florian-Rodriguez, Maria; Chin, Kristi; Hamner, Jennifer J.; Acevedo, Jesús F.; Keller, Patrick W.; Word, R. Ann

doi:10.1038/s41598-019-48527-0

Cited by 11 publications

(6 citation statements)

References 43 publications

(64 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After title and abstract screening, 35 studies met our selection criteria. After studying the full‐text articles, 14 studies (12 animal studies and two human studies) remained 20–33 . From 14 studies, 11 studies were included in the meta‐analyses which included a total of 889 female animals and 197 women in 134 comparisons across eight outcomes.…”

Section: Resultsmentioning

confidence: 99%

“…After studying the full‐text articles, 14 studies (12 animal studies and two human studies) remained. 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 From 14 studies, 11 studies were included in the meta‐analyses which included a total of 889 female animals and 197 women in 134 comparisons across eight outcomes.…”

Section: Resultsmentioning

confidence: 99%

“…Three studies of this systematic review were not included for meta‐analyses: (1) Rodriguez et al 25 was excluded because it reported only on fibulin‐5, which is a matricellular glycoprotein that promotes elastogenesis and inhibits the matrix degrading protein, MMP‐9. For this systematic review, this outcome measure was too indirect to represent wound healing.…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

The effects of oestrogen on vaginal wound healing: A systematic review and meta‐analysis

Vodegel

Kastelein

Jansen

et al. 2021

Neurourology and Urodynamics

View full text Add to dashboard Cite

Aims: To determine the effects of oestrogen or oestrogen deprivation on vaginal wound healing. Impaired wound healing following prolapse surgery may increase the risk of recurrent prolapse in the future. Vaginal oestrogen therapy may improve wound healing, hereby possibly improving surgical outcomes.Methods: A systematic search of OVID MEDLINE, OVID Embase, and Web of Science was conducted up to January 28, 2020. We included original studies comparing wound healing-related outcomes of oestrogen exposed subjects (female animals and women) to hypo-oestrogenic subjects after vaginal surgery. Data on wound healing-related outcome measures were extracted. For each individual comparison, the standardised mean difference (Hedges' g; SMD) and 95% confidence interval (CI) were calculated.Results: Of the 1474 studies reviewed, 14 studies were included for review, and 11 provided data for meta-analysis. Oestrogen improves neovascularisation (SMD: 1.13, 95% CI: 0.67-1.60), microscopic wound closure (SMD: 0.98, 95% CI: 0.66-1.29), collagen synthesis (SMD: 1.08, 95% CI: 0.42-1.74), and tissue strength (SMD: 1.26, 95% CI: 0.53-1.99) in animals. Oestrogen increases granulation (SMD: 1.67, 95% CI: 0.54-2.79) and accelerates macroscopic wound closure (SMD: 1.82, 95% CI: 1.22-2.42) in women and animals. Oestrogen decreases the inflammatory response (SMD: −0.58, 95% CI: −1.14 to −0.02) in women and animals and reduces levels of transforming growth

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The effects of oestrogen on vaginal wound healing: A systematic review and meta‐analysis

Vodegel

Kastelein

Jansen

et al. 2021

Neurourology and Urodynamics

View full text Add to dashboard Cite

show abstract

“…Actinonin at time of vaginal injury alters FBLN5 content in the postpartum vaginal wall. Previously, we showed that a broad-spectrum MMP inhibitor (actinonin) blocked injury-mediated degradation of vaginal FBLN5 in nonpregnant rats after surgical injury 15 . Having established low levels of FBLN5 protein in the parturient vagina, we quantified the effects of actinonin on recovery of FBLN5 after delivery (Fig.…”

Section: Effect Of Simulated Obstetrical Injury On Postpartum Recovermentioning

confidence: 99%

Protease Inhibition Improves Healing of The Vaginal Wall after Obstetrical Injury: Results from a Preclinical Animal Model

Hamner

Florian-Rodriguez

Acevedo

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

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. Pregnancy and vaginal delivery are known independent risk factors for development of pelvic organ prolapse (POP) 1,2. Literature is conflicting as to whether second-degree, or greater, obstetrical lacerations contribute to development of symptomatic POP 3,4. Nonetheless, operative vaginal deliveries, which have a higher risk of obstetrical laceration, are known to confer higher risk for POP than spontaneous vaginal delivery 5. As more data accumulate regarding poor long term outcomes from POP surgical interventions 6,7. understanding the pathogenesis of prolapse and recovery of the pelvic floor after vaginal delivery are important in developing preventative measures. The vaginal wall is comprised of epithelium, the subepithelial lamina propria, smooth muscle (muscularis), and adventitia. Vaginal extracellular matrix is composed of collagen and elastin fibers and smooth muscle 1. Dysfunction or disruption of these components and/or the skeletal muscle structure of the pelvic floor have been linked with POP development 8. Limited data exist regarding pregnancy and parturition-induced changes in the vaginal wall matrix and its mechanical properties. Knockout of Fibulin-5 (FBLN5), a matricellular glycoprotein protein that promotes elastogenesis in the female reproductive tract 9,10 , results in prolapse in mice 11,12. Drewes et al. demonstrated an eightfold decrease in vaginal FBLN5 during pregnancy in mice 8. Further, biomechanical properties of the vagina in pregnant mice included increased distensibility and decreased stiffness relative the vaginal wall of nonpregnant animals 13. The deleterious effects of pregnancy and vaginal delivery on the vaginal matrix have been previously linked to decreased expression of FBLN5 and concomitant upregulation of MMP-9 (a ma...

show abstract

“…Indeed, the expression of FBLN5/Fibulin-5 is low in patients with POP [ 14 ]. FBLN5 modulates endothelial cell adhesion, cell growth, and motility, and is crucial for elastic fiber formation [ 15 ]. FBLN5 and elastin are mainly expressed in lamina propria and fibromuscular layers of the vagina and uterosacral ligament, but the expression of FBLN5 in uterosacral ligaments was enhanced in women with severe POP resulting in cervical elongation [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Transplantation of bone marrow-derived mesenchymal stem cells with silencing of microRNA-138 relieves pelvic organ prolapse through the FBLN5/IL-1β/elastin pathway

Zhao

Sun

Yang

et al. 2021

Aging

View full text Add to dashboard Cite

Nondegradable transvaginal polypropylene meshes for treating pelvic organ prolapse (POP) are now generally unavailable or banned due to serious adverse events. New tissue engineering approaches combine degradable scaffolds with mesenchymal stem/stromal cells from human endometrium (eMSC). In this study, we investigate effect of microRNA-138 (miR-138) regulation on bone marrow-derived mesenchymal stem cells (BMSCs) and the efficacy of BMSC transplantation therapy in a rat POP model. We first identified FBLN5 as a target of miR-138. miR-138, fibulin-5 (FBLN5), interleukin-1β (IL-1β), and elastin expression in uterosacral ligament of POP patients and controls were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. After isolation and identification, BMSCs were treated to alter their expression of miR-138 or FBLN5. Proliferation of BMSCs was analyzed by CCK-8. After establishing the rat pelvic floor dysfunction (PFD) model, we evaluated efficacy of BMSC injection by applying leak point pressure (LPP) and the conscious cystometry (CMG) tests. miR-138 inhibition resulted in increased viability of BMSCs and elevated their secretion of elastin, while downregulating IL-1β expression. BMSCs with inhibited miR-138 improved LPP and conscious CMG results in vivo . Taken together, miR-138 could be a potential therapeutic target for treating POP in conjunction with tissue engineering.

show abstract

Effect of Protease Inhibitors in Healing of the Vaginal Wall

Cited by 11 publications

References 43 publications

The effects of oestrogen on vaginal wound healing: A systematic review and meta‐analysis

The effects of oestrogen on vaginal wound healing: A systematic review and meta‐analysis

Protease Inhibition Improves Healing of The Vaginal Wall after Obstetrical Injury: Results from a Preclinical Animal Model

Transplantation of bone marrow-derived mesenchymal stem cells with silencing of microRNA-138 relieves pelvic organ prolapse through the FBLN5/IL-1β/elastin pathway

Contact Info

Product

Resources

About