Amaral, AnaFernandes, CarinaRebordão, Maria RosaSzóstek-Mioduchowska, AnnaLukasik, KarolinaGawronska-Kozak, BarbaraGama, LuisSkarzynski, Dariusz J.Ferreira-Dias, Graça2022-04-182022-04-182020-05-16Amaral A, Fernandes C, Rebordao MR, Szostek-Mioduchowska A, Lukasik K, Lukasik K, Gawronska-Kozak B, Gama LT, Skarzynski DJ, Ferreira-Dias, G . 2020. The In vitro inhibitory effect of sivelestat on elastase induced collagen and metallopeptidase expression in equine endometrium. Animals, 10(5):863. Doi: 10.3390/ani100508632076-2615http://hdl.handle.net/10400.5/24097Research Areas: Agriculture ; Veterinary Sciences ; ZoologyAbstract: 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.engEndometrosisMareElastaseSivelestatCollagenMetallopeptidasesEndometriumNeutrophil extracellular traps (NETs)journal article10.3390/ani10050863