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The inhibition of Cathepsin G on endometrial explants with endometrosis in the mare

2020-10-30Journal article Open access
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dc.contributor.authorAmaral, Ana
dc.contributor.authorFernandes, Carina
dc.contributor.authorFaes Morazzo, Sofia
dc.contributor.authorRebordão, Maria Rosa
dc.contributor.authorSzóstek-Mioduchowska, Anna
dc.contributor.authorLukasik, Karolina
dc.contributor.authorGawronska-Kozak, Barbara
dc.contributor.authorGama, Luis
dc.contributor.authorJan Skarzynski, Dariusz
dc.contributor.authorFerreira-Dias, Graça
dc.date.accessioned2022-04-18T13:40:40Z
dc.date.available2022-04-18T13:40:40Z
dc.date.issued2020-10-30
dc.descriptionResearch Areas: Veterinary Sciencespt_PT
dc.description.abstractAlthough proteases found in neutrophil extracellular traps (NETs) have antimicrobial properties, they also stimulate collagen type 1 (COL1) production by the mare endometrium, contributing for the development of endometrosis. Cathepsin G (CAT), a protease present in NETs, is inhibited by specific inhibitors, such as cathepsin G inhibitor I (INH; beta-keto-phosphonic acid). Matrix metallopeptidases (MMPs) are proteases involved in the equilibrium of the extracellular matrix. The objective of this study was to investigate the effect of CAT and INH (a selective CAT inhibitor) on the expression of MMP-2 and MMP-9 and on gelatinolytic activity. In addition, the putative inhibitory effect of INH on CAT-induced COL1 production in mare endometrium was assessed. Endometrial explants retrieved from mares in follicular phase or midluteal phase were treated for 24 or 48 h with CAT, inhibitor alone, or both treatments. In explants, transcripts (quantitative polymerase chain reaction) of COL1A2, MMP2, and MMP9, as well as the relative abundance of COL1 protein (Western blot), and activity of MMP-2 and MMP-9 (zymography) were evaluated. The protease CAT induced COL1 expression in explants, at both estrous cycle phases and treatment times. The inhibitory effect of INH was observed on COL1A2 transcripts in follicular phase at 24-h treatment, and in midluteal phase at 48 h (P < 0.05), and on the relative abundance of COL protein in follicular phase and midluteal phase explants, at 48 h (P < 0.001). Our study suggests that MMP-2 might also be involved in an earlier response to CAT, and MMP-9 in a later response, mainly in the follicular phase. While the use of INH reduced CAT-induced COL1 endometrial expression, MMPs might be involved in the fibrogenic response to CAT. Therefore, in mare endometrium, the use of INH may be a future potential therapeutic means to reduce CAT-induced COL1 formation and to hamper endometrosis establishment.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationAmaral A, Fernandes C, Morazzo S, Rebordão MR, Szóstek-Mioduchowska A, Lukasik K, Gawronska-Kozak B, Telo da Gama L, Skarzynski DJ and Ferreira-Dias G. 2020. The inhibition of Cathepsin G on endometrial explants with endometrosis in the mare. Frontiers in Veterinary Science, 7:582211. Doi: 10.3389/fvets.2020.582211pt_PT
dc.identifier.doi10.3389/fvets.2020.582211pt_PT
dc.identifier.eissn2297-1769
dc.identifier.urihttp://hdl.handle.net/10400.5/24095
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherFrontiers, Media SApt_PT
dc.relationUIDP/CVT/00276/2020pt_PT
dc.relation2019/35/D/NZ9/02989pt_PT
dc.relation.publisherversionhttps://www.frontiersin.org/articles/10.3389/fvets.2020.582211/fullpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectEndometrosispt_PT
dc.subjectCathepsin Gpt_PT
dc.subjectCathepsin G inhibitorpt_PT
dc.subjectFibrosispt_PT
dc.subjectMetallopeptidasespt_PT
dc.titleThe inhibition of Cathepsin G on endometrial explants with endometrosis in the marept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FCVT-REP%2F4202%2F2014/PT
oaire.citation.conferencePlaceLausanne, Switzerlandpt_PT
oaire.citation.titleFrontiers in Veterinary Sciencept_PT
oaire.citation.volume7:582211pt_PT
oaire.fundingStream3599-PPCDT
person.familyNameAmaral
person.familyNameFaes Morazzo
person.familyNameRebordão Cordeiro Simões Crisóstomo
person.familyNameGama
person.familyNameLeitão Ferreira-Dias
person.givenNameAna
person.givenNameSofia
person.givenNameMaria Rosa
person.givenNameLuis
person.givenNameGraça Maria
person.identifier.ciencia-idEB18-9420-421B
person.identifier.ciencia-id9515-257A-B35D
person.identifier.ciencia-idC71D-140F-E876
person.identifier.ciencia-idF51C-7F45-C720
person.identifier.orcid0000-0002-0075-262X
person.identifier.orcid0000-0001-6864-5209
person.identifier.orcid0000-0002-4389-445X
person.identifier.orcid0000-0003-3894-3488
person.identifier.orcid0000-0003-0622-6513
person.identifier.ridN-4172-2018
person.identifier.scopus-author-id56394000500
person.identifier.scopus-author-id36027387300
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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