ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014
Adenosine 2A receptor promotes collagen production by human fibroblasts via pathways involving cyclic AMP and AKT but independent of Smad2/3.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 67 citations in OpenAlex.
- Pulsed Electromagnetic Field Exposure Attenuates Ultraviolet B-Induced Dermal Collagen Loss in Association with A2A Adenosine Receptor Signaling.International journal of molecular sciences · 2026Article
- Dynamic Proteomic and Metabolomic Analysis Reveals Metabolic Reprogramming During Early Neuronal Transdifferentiation of Human Fibroblasts Driven by Forskolin.Current issues in molecular biology · 2026Article
- ADA2-Functionalized OMVs Remodel the Tumor Microenvironment in Pancreatic Cancer.Pharmaceutics · 2026Article
- Dual Action of Dipyridamole in Experimental Rheumatoid Arthritis: Suppression of Joint Inflammation and Upregulation of Muscle Anabolism via Adenosine and AMPK Pathways.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Hyaluronic Acid Fillers Versus Polynucleotides for Under-Eye Rejuvenation.Journal of clinical medicine · 2026Review
- Regenerative Approaches to Enhance the Skin Microenvironment and Boost Aesthetic Efficacy: A Narrative Review.International journal of molecular sciences · 2026Review
- Hyaluronic Acid-like Skin Plumping and Radiance Benefits of aMarine drugs · 2026Article
- Endothelial adenosine receptor 2A loss alleviates diabetic vascular calcification by blocking CREB1-SNAI1-driven EndMT.Pharmacological research · 2025Article
- Targeting adenosine 2A receptor signaling suppresses vascular calcification by restraining smooth muscle osteogenic differentiation.Pharmacological research · 2025Article
- Polynucleotides Enhance Collagen Synthesis via Modulating Phosphoenolpyruvate Carboxykinase 1 in Senescent Macrophages: Experimental Evidence.International journal of molecular sciences · 2025Article
- Inhibition of adenosine/A2A receptor signaling suppresses dermal fibrosis by enhancing fatty acid oxidation.Cell communication and signaling : CCS · 2025Article
- Epigallocatechin Gallate inPharmaceuticals (Basel, Switzerland) · 2025Article
- Versatile and Marvelous Potentials of Polydeoxyribonucleotide for Tissue Engineering and Regeneration.Biomaterials research · 2025Review
- The Essential Role of Angiogenesis in Adenosine 2A Receptor Deficiency-mediated Impairment of Wound Healing Involving c-Ski via the ERK/CREB Pathways.International journal of biological sciences · 2024Article
- The Role of Cyclic Adenosine Monophosphate (cAMP) in Modulating Glucocorticoid Receptor Signaling and Its Implications on Glucocorticoid-Related Collagen Loss.International journal of molecular sciences · 2023Article
- Preclinical Models and Promising Pharmacotherapeutic Strategies in Liver Fibrosis: An Update.Current issues in molecular biology · 2023Review
- Hydrogel delivery of purinergic enzymes improves cardiac ischemia/reperfusion injury.Journal of molecular and cellular cardiology · 2023Article
- Biglycan Involvement in Heart Fibrosis: Modulation of Adenosine 2A Receptor Improves Damage in Immortalized Cardiac Fibroblasts.International journal of molecular sciences · 2023Article
- Adenosine and Adenosine Receptors: Advances in Atrial Fibrillation.Biomedicines · 2022Review
- Adenosine receptor signalling in Alzheimer's disease.Purinergic signalling · 2022Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Activation of adenosine A2A receptor (A2AR) promotes fibrosis and collagen synthesis. However, the underlying mechanism is still unclear, not least because cAMP, its principal effector, has been found to inhibit TGFβ1-induced collagen synthesis. Here, we show that in primary normal human dermal fibroblasts, A2AR stimulation with CGS21680 elicits a modest cAMP increase (150 ± 12% of control; EC50 54.8 nM), which stimulates collagen1 (Col1) and collagen3 (Col3), but maximal cAMP resulting from direct activation of adenylyl cyclase by forskolin (15,689 ± 7038% of control; EC50 360.7 nM) inhibits Col1 and increases Col3. Similar to Col1 expression, fibroblast proliferation increased following physiological cAMP increases by CGS21680 but was inhibited by cAMP increases beyond the physiological range by forskolin. The A2AR-mediated increase of Col1 and Col3 was mediated by AKT, while Col3, but not Col1, expression was dependent on p38 and repressed by ERK. TGFβ1 induced phosphorylation of Smad2/3 and increased Col3 expression, which was prevented by Smad3 depletion. In contrast, CGS21680 did not activate Smad2/3, and Smad2/3 knockdown did not prevent CGS21680-induced Col1 or Col3 increases. Our results indicate that cAMP is a concentration-dependent switch for collagen production via noncanonical, AKT-dependent, Smad2/3-independent signaling. These observations explain the paradoxical effects of cAMP on collagen expression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.