The Inhibitory Effect of Noscapine on the In Vitro Cathepsin G-Induced Collagen Expression in Equine Endometrium.
Abstract: Cathepsin G (CAT) is a protease released by neutrophils when forming neutrophil extracellular traps that was already associated with inducing type I collagen (COL1) in equine endometrium in vitro. Endometrosis is a fibrotic condition mainly characterized by COL1 deposition in the equine endometrium. The objective was to evaluate if noscapine (an alkaloid for cough treatment with anti-neoplastic and anti-fibrotic properties) would reduce transcription (evaluated by qPCR) and COL1 protein relative abundance (evaluated by western blot) induced by CAT in equine endometrial explants from follicular and mid-luteal phases treated for 24 or 48 h. The explants treated with CAT increased COL1 expression. Noscapine decreased transcription at both estrous cycle phases, but COL1 relative protein only at the follicular phase, both induced by CAT. Additionally, the noscapine anti-fibrotic action was found to be more effective in the follicular phase. The CAT treatment caused more fibrosis at the longest period of treatment, while noscapine acted better at the shortest time of treatment. Our results showed that noscapine could act as an anti-fibrotic drug in equine endometrosis by inhibiting CAT in vitro. Noscapine offers a new promising therapeutic tool for treating fibrosis as a single non-selective agent to be considered in the future.
Publication Date: 2021-10-19 PubMed ID: 34685478PubMed Central: PMC8539599DOI: 10.3390/life11101107Google Scholar: Lookup
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Summary
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This research is about the anti-fibrotic impact of noscapine, a cough treatment alkaloid, on equine endometrosis by inhibiting the action of cathepsin G, a protease associated with inducing type I collagen, in vitro.
Objective and Background
- The primary objective of this study was to determine whether noscapine, an alkaloid primarily used in cough treatment, can reduce the transcription and abundance of type I collagen (COL1) protein induced by Cathepsin G (CAT) in horse endometrial explants. This investigation is significant as CAT is a protease released by neutrophils, known for inducing COL1 in the equine endometrium.
- Endometrosis in horses is a fibrotic condition mainly characterized by the deposition of COL1 in the endometrium. Consequentially, any substance capable of reducing COL1 levels could potentially serve as an anti-fibrotic drug in equine endometrosis.
Methodology and Findings
- The research used equine endometrial explants from the follicular and mid-luteal phases, treating them for 24 or 48 hours. When these explants were treated with CAT, it increased the expression of COL1.
- However, when treated with noscapine, the transcription was observed to reduce in both estrous cycle phases. In contrast, the relative protein of COL1 dropped only during the follicular phase.
- Additionally, it was found that the anti-fibrotic action of noscapine was more effective during the follicular phase.
- On examining the duration of the treatment, more fibrosis was identified when treated with CAT for an extended period while noscapine was found to be most effective when administered for a shorter duration.
Conclusion
- The results clearly demonstrated that noscapine can function as an anti-fibrotic agent for equine endometrosis by inhibiting the action of CAT in vitro. As such, it presents a promising therapeutic tool for treating fibrosis.
- Moreover, it can be employed as a single non-selective agent for future treatments, thus broadening the scope of its application and indicating a positive outlook in controlling and managing fibrotic conditions, not just in equine endometrosis but potentially in other areas as well.
Cite This Article
APA
Amaral A, Fernandes C, Szóstek-Mioduchowska A, Lukasik K, Rebordão MR, Pinto-Bravo P, Skarzynski DJ, Ferreira-Dias G.
(2021).
The Inhibitory Effect of Noscapine on the In Vitro Cathepsin G-Induced Collagen Expression in Equine Endometrium.
Life (Basel), 11(10), 1107.
https://doi.org/10.3390/life11101107 Publication
Researcher Affiliations
- CIISA-Centro de Investigação Interdisciplinar em Sanidade Animal, Departamento de Morfologia e Função, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, Portugal.
- CIISA-Centro de Investigação Interdisciplinar em Sanidade Animal, Departamento de Morfologia e Função, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, Portugal.
- Institute of Animal Reproduction and Food Research, Polish Academy of Science, 10-748 Olsztyn, Poland.
- Institute of Animal Reproduction and Food Research, Polish Academy of Science, 10-748 Olsztyn, Poland.
- CIISA-Centro de Investigação Interdisciplinar em Sanidade Animal, Departamento de Morfologia e Função, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, Portugal.
- Polytechnic of Coimbra, Coimbra Agriculture School, Bencanta, 3045-601 Coimbra, Portugal.
- Polytechnic of Coimbra, Coimbra Agriculture School, Bencanta, 3045-601 Coimbra, Portugal.
- Institute of Animal Reproduction and Food Research, Polish Academy of Science, 10-748 Olsztyn, Poland.
- CIISA-Centro de Investigação Interdisciplinar em Sanidade Animal, Departamento de Morfologia e Função, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, Portugal.
Grant Funding
- PPN/BIL/2018/1/00250/U/0001 / Narodowa Agencja Wymiany Akademickiej
- UIDB/00276/2020 / Fundau00e7u00e3o para a Ciu00eancia e Tecnologia
- PTDC/CVT-REP/4202/2014 / Fundau00e7u00e3o para a Ciu00eancia e Tecnologia
- SFRH/BD/101058/2014 / Fundau00e7u00e3o para a Ciu00eancia e Tecnologia
Conflict of Interest Statement
The authors declare no conflict of interest.
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Citations
This article has been cited 1 times.- Amaral A, Cebola N, Szóstek-Mioduchowska A, Rebordão MR, Kordowitzki P, Skarzynski D, Ferreira-Dias G. Inhibition of Myeloperoxidase Pro-Fibrotic Effect by Noscapine in Equine Endometrium.. Int J Mol Sci 2023 Feb 10;24(4).
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