The Inhibitory Effect of Noscapine on the In Vitro Cathepsin G-Induced Collagen Expression in Equine Endometrium

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....

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Main Authors: Ana Amaral, Carina Fernandes, Anna Szóstek-Mioduchowska, Karolina Lukasik, Maria Rosa Rebordão, Pedro Pinto-Bravo, Dariusz Jan Skarzynski, Graça Ferreira-Dias
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:Life
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Online Access:https://www.mdpi.com/2075-1729/11/10/1107
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author Ana Amaral
Carina Fernandes
Anna Szóstek-Mioduchowska
Karolina Lukasik
Maria Rosa Rebordão
Pedro Pinto-Bravo
Dariusz Jan Skarzynski
Graça Ferreira-Dias
author_facet Ana Amaral
Carina Fernandes
Anna Szóstek-Mioduchowska
Karolina Lukasik
Maria Rosa Rebordão
Pedro Pinto-Bravo
Dariusz Jan Skarzynski
Graça Ferreira-Dias
author_sort Ana Amaral
collection DOAJ
description 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 <i>COL1A2</i> 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 <i>COL1A2</i> 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.
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spelling doaj.art-f8f5b65fe4f242d9889f44563c52fb172023-11-22T18:53:42ZengMDPI AGLife2075-17292021-10-011110110710.3390/life11101107The Inhibitory Effect of Noscapine on the In Vitro Cathepsin G-Induced Collagen Expression in Equine EndometriumAna Amaral0Carina Fernandes1Anna Szóstek-Mioduchowska2Karolina Lukasik3Maria Rosa Rebordão4Pedro Pinto-Bravo5Dariusz Jan Skarzynski6Graça Ferreira-Dias7CIISA—Centro de Investigação Interdisciplinar em Sanidade Animal, Departamento de Morfologia e Função, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, PortugalCIISA—Centro de Investigação Interdisciplinar em Sanidade Animal, Departamento de Morfologia e Função, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, PortugalInstitute of Animal Reproduction and Food Research, Polish Academy of Science, 10-748 Olsztyn, PolandInstitute of Animal Reproduction and Food Research, Polish Academy of Science, 10-748 Olsztyn, PolandCIISA—Centro de Investigação Interdisciplinar em Sanidade Animal, Departamento de Morfologia e Função, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, PortugalPolytechnic of Coimbra, Coimbra Agriculture School, Bencanta, 3045-601 Coimbra, PortugalInstitute of Animal Reproduction and Food Research, Polish Academy of Science, 10-748 Olsztyn, PolandCIISA—Centro de Investigação Interdisciplinar em Sanidade Animal, Departamento de Morfologia e Função, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, PortugalCathepsin 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 <i>COL1A2</i> 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 <i>COL1A2</i> 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.https://www.mdpi.com/2075-1729/11/10/1107equineendometrosisfibrosiscollagencathepsin Gnoscapine
spellingShingle Ana Amaral
Carina Fernandes
Anna Szóstek-Mioduchowska
Karolina Lukasik
Maria Rosa Rebordão
Pedro Pinto-Bravo
Dariusz Jan Skarzynski
Graça Ferreira-Dias
The Inhibitory Effect of Noscapine on the In Vitro Cathepsin G-Induced Collagen Expression in Equine Endometrium
Life
equine
endometrosis
fibrosis
collagen
cathepsin G
noscapine
title The Inhibitory Effect of Noscapine on the In Vitro Cathepsin G-Induced Collagen Expression in Equine Endometrium
title_full The Inhibitory Effect of Noscapine on the In Vitro Cathepsin G-Induced Collagen Expression in Equine Endometrium
title_fullStr The Inhibitory Effect of Noscapine on the In Vitro Cathepsin G-Induced Collagen Expression in Equine Endometrium
title_full_unstemmed The Inhibitory Effect of Noscapine on the In Vitro Cathepsin G-Induced Collagen Expression in Equine Endometrium
title_short The Inhibitory Effect of Noscapine on the In Vitro Cathepsin G-Induced Collagen Expression in Equine Endometrium
title_sort inhibitory effect of noscapine on the in vitro cathepsin g induced collagen expression in equine endometrium
topic equine
endometrosis
fibrosis
collagen
cathepsin G
noscapine
url https://www.mdpi.com/2075-1729/11/10/1107
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