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Home / Equine Research Bank / Animals (Basel) / The In Vitro Inhibitory Effect of Sivelestat on Elastase Ind...
Animals : an open access journal from MDPI2020; 10(5); 863; doi: 10.3390/ani10050863

The In Vitro Inhibitory Effect of Sivelestat on Elastase Induced Collagen and Metallopeptidase Expression in Equine Endometrium.

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 effects of ELA and sivelestat (selective elastase inhibitor) on MMP-2 and MMP-9 expression and gelatinolytic activity, as well as the potential inhibitory effect 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 , 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 mRNA transcription (24 h) in active MMP-2 (48 h), both in FP, and in transcripts in FP (48 h) and MLP (24 h) ( < 0.05). Sivelestat inhibited ELA-induced transcripts in FP (24 h) and MLP (24 h, 48 h) ( < 0.05). The sivelestat inhibitory effect was detected in 9 transcripts in FP at 48 h ( < 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.
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Publication Date: 2020-05-16 PubMed ID: 32429399PubMed Central: PMC7278485DOI: 10.3390/ani10050863Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study investigates the effects of an elastase inhibitor called sivelestat on collagen and metallopeptidase expression possibly related to endometritis in horses. The main findings suggest that sivelestat may slow down the development of endometrosis by reducing collagen deposition induced by elastase.

Objective and Scope of the Study

  • The research is aimed at exploring the effects of elastase (ELA) and a specific elastase inhibitor, sivelestat, on the expression and activity of metallopeptidases (MMP-2 and MMP-9), and collagen type I (COL1) in equine endometrium.
  • The study also seeks to ascertain the potential inhibitory impacts of sivelestat on ELA-induced COL1 in horse’s endometrium.

Methodology

  • Endometrial explants from two different phases – the follicular phase (FP) and the mid-luteal phase (MLP) – were treated for either 24 or 48 hours with ELA, sivelestat, or a combination of both.
  • The expressions of MMP2 and MMP9 were evaluated using qPCR, the relative abundance of COL1 protein was determined through Western blot, and gelatinolytic activity of MMP-2 and MMP-9 were assessed via zymography.

Findings

  • The treatment with ELA resulted in increased mRNA transcription and active MMP-2, particularly in the FP. Moreover, FP and MLP both showed elevated levels of COL1 transcripts.
  • Sivelestat was found to inhibit ELA-induced COL1 transcripts in both FP and MLP.
  • However, despite the inhibitory effect of sivelestat observed in the MMP9 transcripts in FP, it didn’t lead to a change in protease activity.

Conclusion

  • The study concludes that MMP-2 and MMP-9 might contribute to the fibrotic response of the endometrium to ELA, possibly leading to endometrosis, a fibrotic condition affecting the lining of the uterus in mares.
  • The inhibitory effect of sivelestat on ELA-induced COL1 suggests its potential use in reducing COL1 deposition and preventing the development of endometrosis in the mare’s endometrium.

Cite This Article

APA
Amaral A, Fernandes C, Rebordão MR, Szóstek-Mioduchowska A, Lukasik K, Gawronska-Kozak B, Telo da Gama L, Skarzynski DJ, Ferreira-Dias G. (2020). The In Vitro Inhibitory Effect of Sivelestat on Elastase Induced Collagen and Metallopeptidase Expression in Equine Endometrium. Animals (Basel), 10(5), 863. https://doi.org/10.3390/ani10050863

Publication

Animals : an open access journal from MDPI
ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 10
Issue: 5
PII: 863

Researcher Affiliations

Amaral, Ana
  • CIISA-Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, Portugal.
Fernandes, Carina
  • CIISA-Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, Portugal.
Rebordão, Maria Rosa
  • CIISA-Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, Portugal.
  • Coimbra College of Agriculture, Polytechnic Institute of Coimbra, 3045-601 Coimbra, Portugal.
Szóstek-Mioduchowska, Anna
  • Institute of Animal Reproduction and Food Research, Polish Academy of Science,10-748 Olsztyn, Poland.
Lukasik, Karolina
  • Institute of Animal Reproduction and Food Research, Polish Academy of Science,10-748 Olsztyn, Poland.
Gawronska-Kozak, Barbara
  • Institute of Animal Reproduction and Food Research, Polish Academy of Science,10-748 Olsztyn, Poland.
Telo da Gama, Luís
  • CIISA-Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, Portugal.
Skarzynski, Dariusz J
  • Institute of Animal Reproduction and Food Research, Polish Academy of Science,10-748 Olsztyn, Poland.
Ferreira-Dias, Graça
  • CIISA-Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, Portugal.

Grant Funding

  • PTDC/CVT-REP/4202/2014 / Fundau00e7u00e3o para a Ciu00eancia e Tecnologia
  • UIDP/CVT/00276/2019 / Fundau00e7u00e3o para a Ciu00eancia e Tecnologia
  • SFRH/BD/101058/2014 / Fundau00e7u00e3o para a Ciu00eancia e Tecnologia
  • No. PPN/BIL/2018/1/00250/U/0001 / NAWA, Poland and Fundau00e7u00e3o para a Ciu00eancia e Tecnologia, Portugal

Conflict of Interest Statement

The authors declare that there are no conflict of interest.

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Citations

This article has been cited 6 times.
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