Document details

The In vitro inhibitory effect of sivelestat on elastase induced collagen and metallopeptidase expression in equine endometrium

Author(s): Amaral, Ana ; Fernandes, Carina ; Rebordão, Maria Rosa ; Szóstek-Mioduchowska, Anna ; Lukasik, Karolina ; Gawronska-Kozak, Barbara ; Gama, Luis ; Skarzynski, Dariusz J. ; Ferreira-Dias, Graça

Date: 2020

Persistent ID: http://hdl.handle.net/10400.5/24097

Origin: Repositório da Universidade de Lisboa

Project/scholarship: info:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FCVT-REP%2F4202%2F2014/PT; info:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F101058%2F2014/PT;

Subject(s): Endometrosis; Mare; Elastase; Sivelestat; Collagen; Metallopeptidases; Endometrium; Neutrophil extracellular traps (NETs)


Description

Research Areas: Agriculture ; Veterinary Sciences ; Zoology

Abstract: Neutrophil extracellular traps (NETs) fight endometritis, and elastase (ELA), a protease found in NETs, might induce collagen type I (COL1) accumulation in equine endometrium. Metallopeptidases (MMPs) are involved in extracellular matrix balance. The aim was to evaluate the e ects of ELA and sivelestat (selective elastase inhibitor) on MMP-2 and MMP-9 expression and gelatinolytic activity, as well as the potential inhibitory e ect of sivelestat on ELA-induced COL1 in equine endometrium. Endometrial explants from follicular (FP) and mid-luteal (MLP) phases were treated for 24 or 48 h with ELA, sivelestat, and their combination. Transcripts of COL1A2, MMP2, and MMP9 were evaluated by qPCR; COL1 protein relative abundance by Western blot, and MMP-2 and MMP-9 gelatinolytic activity by zymography. In response to ELA treatment, there was an increase in MMP2 mRNA transcription (24 h) in active MMP-2 (48 h), both in FP, and in MMP9 transcripts in FP (48 h) and MLP (24 h) (p < 0.05). Sivelestat inhibited ELA-induced COL1A2 transcripts in FP (24 h) and MLP (24 h, 48 h) (p < 0.05). The sivelestat inhibitory e ect was detected in MMP9 transcripts in FP at 48 h (p < 0.05), but proteases activity was unchanged. Thus, MMP-2 and MMP-9 might be implicated in endometrium fibrotic response to ELA. In mare endometrium, sivelestat may decrease ELA-induced COL1 deposition and hinder endometrosis development.

Document Type Journal article
Language English
Contributor(s) Repositório da Universidade de Lisboa
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