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Background and Purpose: Adenosine A2A receptor stimulation promotes the synthesis of collagen type I and type III (Col1 and Col3), mediators of fibrosis and scarring. The A2A receptor modulates collagen balance via cAMP/PKA/p38-MAPK/Akt pathways. Wnt signalling is important in fibrosis and the cAMP and Wnt pathways converge. Because the A2A receptor is Gs-linked and increases cAMP, we determined whether A2A receptors and Wnt signalling interact.Experimental Approach: Total β-catenin, de-phosphorylated β-catenin (canonical activation, de-phospho β-catenin) and phosphorylated β-catenin at Ser552 (non-canonical activation, p-Ser552 β-catenin) levels were determined in primary human dermal fibroblasts, cytosol and nucleus, by western blot analysis and fluorescence microscopy, before and after stimulation by A2A receptor-selective agonist CGS21680, with/without A2A receptor-selective antagonist (SCH56261) pretreatment. β-Catenin was knocked down by transfection with scrambled-siRNA or specific-siRNA, and Col1 and Col3 levels determined by western blots.Key Results: CGS21680 stimulation rapidly (15 min) increased cellular β-catenin levels. Both de-phospho β-catenin and p-Ser552 β-catenin levels were also increased. CGS21680 stimulated the translocation of total de-phospho and p-Ser552 β-catenin to the nucleus. A2A receptor-stimulation increased Col1 synthesis similarly in β-catenin knockeddown and scrambled cells. However, β-catenin knockdown abolished the increase in Col3 synthesis induced in A2A receptor-stimulated fibroblasts.Conclusions and Implications: A2A receptor stimulation promotes Col3 synthesis via the activation of canonical and non-canonical β-catenin, consistent with a role for A2A receptors in dermal fibrosis and scarring. [ABSTRACT FROM AUTHOR]

Downloaded from http://journals.lww.com/dermatologicsurgery by BhDMf5ePHKbH4TTImqenVA+lpWIIBvonhQl60EtgtdlLYrLzSPu+hQedJnbNaXBf on 03/22/2021 Downloaded from http://journals.lww.com/dermatologicsurgery by BhDMf5ePHKbH4TTImqenVA+lpWIIBvonhQl60EtgtdlLYrLzSPu+hQedJnbNaXBf on 03/22/2021 Althoughweacknowledgeoursmallsamplesize,survey brevity, and the limits of patients' recall ability, our data ultimately suggest that patients favor treatment with the CTA. Theseresultssuggestthatdermatologistsshould use PRP with caution in patients with pre-existing, clinically significant anemia and may consider routine monitoring for patients with a large surface area treated for an extended duration. However,as both techniques are therapeutically effective, 4,5 we urge physicians to consider patient preference when choosing a method. [Extracted from the article]

Background and Purpose: Adenosine A 2A receptor stimulation promotes the synthesis of collagen type I and type III (Col1 and Col3), mediators of fibrosis and scarring. The A 2A receptor modulates collagen balance via cAMP/PKA/p38-MAPK/Akt pathways. Wnt signalling is important in fibrosis and the cAMP and Wnt pathways converge. Because the A 2A receptor is Gs-linked and increases cAMP, we determined whether A 2A receptors and Wnt signalling interact., Experimental Approach: Total β-catenin, de-phosphorylated β-catenin (canonical activation, de-phospho β-catenin) and phosphorylated β-catenin at Ser 552 (non-canonical activation, p-Ser 552 β-catenin) levels were determined in primary human dermal fibroblasts, cytosol and nucleus, by western blot analysis and fluorescence microscopy, before and after stimulation by A 2A receptor-selective agonist CGS21680, with/without A 2A receptor-selective antagonist (SCH56261) pretreatment. β-Catenin was knocked down by transfection with scrambled-siRNA or specific-siRNA, and Col1 and Col3 levels determined by western blots., Key Results: CGS21680 stimulation rapidly (15 min) increased cellular β-catenin levels. Both de-phospho β-catenin and p-Ser 552 β-catenin levels were also increased. CGS21680 stimulated the translocation of total de-phospho and p-Ser 552 β-catenin to the nucleus. A 2A receptor-stimulation increased Col1 synthesis similarly in β-catenin knockeddown and scrambled cells. However, β-catenin knockdown abolished the increase in Col3 synthesis induced in A 2A receptor-stimulated fibroblasts., Conclusions and Implications: A 2A receptor stimulation promotes Col3 synthesis via the activation of canonical and non-canonical β-catenin, consistent with a role for A 2A receptors in dermal fibrosis and scarring., (© 2016 The British Pharmacological Society.)