The Inhibition of Cathepsin G on Endometrial Explants With Endometrosis in the Mare.
Authors: Amaral Ana, Fernandes Carina, Morazzo Sofia, Rebordão Maria Rosa, Szóstek-Mioduchowska Anna, Lukasik Karolina, Gawronska-Kozak Barbara, Telo da Gama Luís, Skarzynski Dariusz Jan, Ferreira-Dias Graça
Journal: Frontiers in veterinary science
Summary
Endometrosis in mares—a condition characterised by abnormal collagen deposition in the uterine lining—is exacerbated by neutrophil extracellular traps (NETs), which release proteases including cathepsin G (CAT) that paradoxically stimulate excessive type 1 collagen (COL1) production despite their antimicrobial function. Researchers treated endometrial tissue samples from mares at different cycle phases with CAT alone, a selective CAT inhibitor (INH), or both treatments, measuring collagen gene and protein expression alongside matrix metallopeptidase (MMP) activity over 24–48 hours. CAT significantly increased COL1 expression in all conditions; critically, INH suppressed this effect in follicular phase samples at 24 hours and luteal phase samples at 48 hours, reducing collagen protein by over 50% at the 48-hour mark across both cycle phases (P < 0.001). The findings suggest that MMP-2 may mount an early protective response to CAT whilst MMP-9 operates later, predominantly during the follicular phase, indicating these enzymes participate in the fibrogenic cascade. For practitioners managing endometrosis, these results indicate that targeted inhibition of cathepsin G could represent a novel therapeutic strategy to interrupt collagen accumulation and potentially slow disease progression, though further in vivo validation is needed before clinical application.
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Practical Takeaways
- •Cathepsin G inhibitors may represent a novel therapeutic strategy to prevent endometrosis development by blocking excessive collagen deposition in the mare endometrium
- •The timing of treatment may matter—inhibitor effects on collagen expression vary between follicular and luteal phases, suggesting cycle-stage-dependent dosing protocols could be optimized
- •Further research is needed to translate these in vitro findings to in vivo efficacy before clinical application in affected mares
Key Findings
- •Cathepsin G (CAT) induced collagen type 1 (COL1) expression in mare endometrial explants at both estrous cycle phases
- •Cathepsin G inhibitor (INH) reduced CAT-induced COL1A2 transcripts at 24 h in follicular phase and 48 h in midluteal phase (P < 0.05)
- •INH significantly reduced relative abundance of COL1 protein in both follicular and midluteal phase explants at 48 h (P < 0.001)
- •MMP-2 and MMP-9 appear to be involved in fibrogenic response to CAT, with MMP-2 responding earlier and MMP-9 responding later