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Opposing Effects of Adenosine and Inosine in Human Subcutaneous Fibroblasts May Be Regulated by Third Party ADA Cell Providers

2020-03-07Journal article Open access
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dc.contributor.authorHerman-de-Sousa, Carina
dc.contributor.authorPinheiro, Ana Rita
dc.contributor.authorParamos-de-Carvalho, Diogo
dc.contributor.authorCosta, Maria Adelina
dc.contributor.authorFerreirinha, Fátima
dc.contributor.authorMagalhães-Cardoso, Teresa
dc.contributor.authorRibeiro, Severino
dc.contributor.authorPelletier, Julie
dc.contributor.authorSévigny, Jean
dc.contributor.authorCorreia-de-Sá, Paulo
dc.date.accessioned2021-11-16T10:45:08Z
dc.date.available2021-11-16T10:45:08Z
dc.date.issued2020-03-07
dc.description.abstractHuman subcutaneous fibroblasts (HSCF) challenged with inflammatory mediators release huge amounts of ATP, which rapidly generates adenosine. Given the nucleoside's putative relevance in wound healing, dermal fibrosis, and myofascial pain, we investigated the role of its precursor, AMP, and of its metabolite, inosine, in HSCF cells growth and collagen production. AMP (30 µM) was rapidly (t½ 3 ± 1 min) dephosphorylated into adenosine by CD73/ecto-5'-nucleotidase. Adenosine accumulation (t½ 158 ± 17 min) in the extracellular fluid reflected very low cellular adenosine deaminase (ADA) activity. HSCF stained positively against A2A and A3 receptors but were A1 and A2B negative. AMP and the A2A receptor agonist, CGS21680C, increased collagen production without affecting cells growth. The A2A receptor antagonist, SCH442416, prevented the effects of AMP and CGS21680C. Inosine and the A3 receptor agonist, 2Cl-IB-MECA, decreased HSCF growth and collagen production in a MRS1191-sensitive manner, implicating the A3 receptor in the anti-proliferative action of inosine. Incubation with ADA reproduced the inosine effect. In conclusion, adenosine originated from extracellular ATP hydrolysis favors normal collagen production by HSCF via A2A receptors. Inhibition of unpredicted inosine formation by third party ADA cell providers (e.g., inflammatory cells) may be a novel therapeutic target to prevent inappropriate dermal remodeling via A3 receptors activation.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationHerman-de-Sousa C, Pinheiro AR, Paramos-de-Carvalho D, et al. Opposing Effects of Adenosine and Inosine in Human Subcutaneous Fibroblasts May Be Regulated by Third Party ADA Cell Providers. Cells. 2020;9(3):651. Published 2020 Mar 7. doi:10.3390/cells9030651pt_PT
dc.identifier.doi10.3390/cells9030651pt_PT
dc.identifier.issn2073-4409
dc.identifier.urihttp://hdl.handle.net/10400.16/2545
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relation.publisherversionhttps://www.mdpi.com/2073-4409/9/3/651pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectadenosine A2A receptorpt_PT
dc.subjectadenosine A3 receptorpt_PT
dc.subjectcells proliferationpt_PT
dc.subjectcollagen productionpt_PT
dc.subjectexchange protein activated by cyclic AMP (EPAC) pathwaypt_PT
dc.subjecthuman subcutaneous fibroblastpt_PT
dc.subjectinosinept_PT
dc.titleOpposing Effects of Adenosine and Inosine in Human Subcutaneous Fibroblasts May Be Regulated by Third Party ADA Cell Providerspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceSwitzerlandpt_PT
oaire.citation.issue3pt_PT
oaire.citation.startPage651pt_PT
oaire.citation.titleCellspt_PT
oaire.citation.volume9pt_PT
person.familyNameCorreia-de-Sá
person.givenNamePaulo
person.identifier6802
person.identifier.ciencia-id1C1B-40EC-3695
person.identifier.orcid0000-0002-6114-9189
person.identifier.ridF-1079-2015
person.identifier.scopus-author-id6603665744
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication65bf40ea-e2ee-42f0-9d13-8b5bfbf2bf1e
relation.isAuthorOfPublication.latestForDiscovery65bf40ea-e2ee-42f0-9d13-8b5bfbf2bf1e

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