The In Vitro Inhibitory Effect of Sivelestat on Elastase Induced Collagen and Metallopeptidase Expression in Equine Endometrium.
Authors: Amaral Ana, Fernandes Carina, Rebordão Maria Rosa, Szóstek-Mioduchowska Anna, Lukasik Karolina, Gawronska-Kozak Barbara, Telo da Gama Luís, Skarzynski Dariusz J, Ferreira-Dias Graça
Journal: Animals : an open access journal from MDPI
Summary
# Editorial Summary During endometritis, neutrophils release elastase as part of their antimicrobial strategy, but this protease may paradoxically trigger excessive collagen deposition and fibrosis in the equine endometrium—a pathological shift towards endometrosis. Researchers cultured endometrial tissue samples from mares at different reproductive stages and exposed them to elastase alone, the selective elastase inhibitor sivelestat alone, or both in combination, then measured collagen type I expression and activity of matrix metallopeptidases (MMP-2 and MMP-9) at 24 and 48 hours using molecular and protein analysis techniques. Elastase significantly upregulated MMP-2 and MMP-9 transcription and increased active MMP-2 protein, suggesting these enzymes respond to elastase-induced tissue remodelling; sivelestat effectively suppressed the elastase-driven increase in collagen type I transcription in both follicular and luteal phase endometrium, though it only partially reduced MMP-9 transcription without affecting enzyme activity. The findings suggest that elastase inhibition could interrupt the fibrotic cascade leading to endometrosis, offering a potential therapeutic avenue for mares suffering recurrent or persistent endometritis where NET-derived elastase contributes to irreversible endometrial damage and reduced fertility.
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Practical Takeaways
- •Elastase inhibition via sivelestat could represent a novel therapeutic strategy to reduce pathological collagen accumulation and fibrosis in equine endometritis cases
- •The cyclical differences between follicular and luteal phases suggest that treatment timing relative to reproductive cycle phase may influence therapeutic efficacy
- •Further in vivo studies are needed to translate these in vitro findings into clinical recommendations for mares with endometrial disease
Key Findings
- •Elastase treatment increased MMP2 mRNA transcription at 24h and active MMP-2 at 48h in follicular phase endometrium (p < 0.05)
- •Sivelestat inhibited elastase-induced COL1A2 transcripts in both follicular phase (24h) and mid-luteal phase (24h, 48h) endometrium (p < 0.05)
- •Sivelestat reduced MMP9 transcripts in follicular phase at 48h (p < 0.05), though protease activity remained unchanged
- •Sivelestat may decrease elastase-induced collagen deposition and potentially prevent endometrosis development in mare endometrium