ArticlePurinergic signalling2013
Adenosine A2A receptor (A2AR) is a fine-tune regulator of the collagen1:collagen3 balance.
Article in Purinergic signalling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Review
- Inhibition of Retinal AdoRA2a Activity Attenuates Myopia Progression.Investigative ophthalmology & visual science · 2026Article
- Review
- Current practices and perceived effectiveness of polynucleotides for treatment of facial erythema by cosmetic physicians.Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) · 2023Article
- Clinical validation of an elastin-derived trifunctional peptide for skin regeneration.American journal of translational research · 2023Article
- The possible role of the nucleoside adenosine in countering skin aging: A review.BioFactors (Oxford, England) · 2022Review
- Polydeoxyribonucleotide for the improvement of a hypertrophic retracting scar-An interesting case report.Journal of cosmetic dermatology · 2020Article
- Intraarticular injection of liposomal adenosine reduces cartilage damage in established murine and rat models of osteoarthritis.Scientific reports · 2020Article
- Article
- Bone Tissue Engineering in the Growing Calvaria Using Dipyridamole-Coated, Three-Dimensionally-Printed Bioceramic Scaffolds: Construct Optimization and Effects on Cranial Suture Patency.Plastic and reconstructive surgery · 2020Article
- Role of Cardiac AFrontiers in pharmacology · 2020Review
- Adenosine AFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Adenosine AThe American journal of pathology · 2017Article
- Article
- Adenosine ABritish journal of pharmacology · 2016Article
- Signaling pathways involving adenosine A2A and A2B receptors in wound healing and fibrosis.Purinergic signalling · 2016Review
- Adenosine A2A receptor plays an important role in radiation-induced dermal injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Purinergic signaling in scarring.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Review
- Apremilast, a novel phosphodiesterase 4 (PDE4) inhibitor, regulates inflammation through multiple cAMP downstream effectors.Arthritis research & therapy · 2015Article
- Adenosine 2A receptor promotes collagen production by human fibroblasts via pathways involving cyclic AMP and AKT but independent of Smad2/3.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Adenosine is a potent endogenous anti-inflammatory and immunosuppressive metabolite that is a potent modulator of tissue repair. However, the adenosine A2A receptor (A2AR)-mediated promotion of collagen synthesis is detrimental in settings such as scarring and scleroderma. The signaling cascade from A2AR stimulation to increased collagen production is complex and obscure, not least because cAMP and its downstream molecules PKA and Epac1 have been reported to inhibit collagen production. We therefore examined A2AR-stimulated signaling for collagen production by normal human dermal fibroblasts (NHDF). Collagen1 (Col1) and collagen3 (Col3) content after A2AR activation by CGS21680 was studied by western blotting. Contribution of PKA and Epac was analyzed by the PKA inhibitor PKI and by knockdowns of the PKA-Cα, -Cβ, -Cγ, Epac1, and Epac2. CGS21680 stimulates Col1 expression at significantly lower concentrations than those required to stimulate Col3 expression. A2AR stimulates Col1 expression by a PKA-dependent mechanism since PKA inhibition or PKA-Cα and -Cβ knockdown prevents A2AR-mediated Col1 increase. In contrast, A2AR represses Col3 via PKA but stimulates both Col1 and Col3 via an Epac2-dependent mechanism. A2AR stimulation with CGS21680 at 0.1 μM increased Col3 expression only upon PKA blockade. A2AR activation downstream signaling for Col1 and Col3 expression proceeds via two distinct pathways with varying sensitivity to cAMP activation; more highly cAMP-sensitive PKA activation stimulates Col1 expression, and less cAMP-sensitive Epac activation promotes both Col1 and Col3 expression. These observations may explain the dramatic change in Col1:Col3 ratio in hypertrophic and immature scars, where adenosine is present in higher concentrations than in normal skin.
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