ArticleAmerican journal of physiology. Cell physiology2009
Regulation of cardiac fibroblast collagen synthesis by adenosine: roles for Epac and PI3K.
Article in American journal of physiology. Cell physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 57 citations in OpenAlex.
- Identification and Verification of Potential Markers Related to Myocardial Fibrosis by Bioinformatics Analysis.Biochemical genetics · 2025Review
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- Reduced adenosine receptor expression in ACS patients with no-reflow phenomenon undergoing primary PCI.Future cardiology · 2025Article
- Off-Target Effects of P2Y12 Receptor Inhibitors: Focus on Early Myocardial Fibrosis Modulation.International journal of molecular sciences · 2023Review
- Extracellular cAMP-Adenosine Pathway Signaling: A Potential Therapeutic Target in Chronic Inflammatory Airway Diseases.Frontiers in immunology · 2022Review
- Exploring the cardiac ECM during fibrosis: A new era with next-gen proteomics.Frontiers in molecular biosciences · 2022Review
- GPCR-mediated YAP/TAZ inactivation in fibroblasts via EPAC1/2, RAP2C, and MAP4K7.Journal of cellular physiology · 2021Article
- Review
- Epac1 deficiency inhibits basic fibroblast growth factor-mediated vascular smooth muscle cell migration.The journal of physiological sciences : JPS · 2019Article
- Exchange protein activated by cyclic-adenosine monophosphate (Epac) regulates atrial fibroblast function and controls cardiac remodelling.Cardiovascular research · 2019Article
- Epac is required for exogenous and endogenous stimulation of adenosine APurinergic signalling · 2018Article
- Hydrostatic pressure suppresses fibrotic changes via Akt/GSK-3 signaling in human cardiac fibroblasts.Physiological reports · 2018Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Adenosine Receptor-Mediated Cardioprotection-Current Limitations and Future Directions.Frontiers in pharmacology · 2018Article
- The role of Epac in the heart.Cellular and molecular life sciences : CMLS · 2017Review
- Stimulation of Adenosine AFrontiers in pharmacology · 2017Article
- Adenosine ADrug design, development and therapy · 2017Article
- Targeting Adenosine Receptors for the Treatment of Cardiac Fibrosis.Frontiers in pharmacology · 2017Review
- Effects of linagliptin and liraglutide on glucose- and angiotensin II-induced collagen formation and cytoskeleton degradation in cardiac fibroblasts in vitro.Acta pharmacologica Sinica · 2016Article
- Signaling pathways involving adenosine A2A and A2B receptors in wound healing and fibrosis.Purinergic signalling · 2016Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Rat cardiac fibroblasts (CF) express multiple adenosine (ADO) receptors. Pharmacological evidence suggests that activation of A(2) receptors may inhibit collagen synthesis via adenylyl cyclase-induced elevation of cellular cAMP. We have characterized the signaling pathways involved in ADO-mediated inhibition of collagen synthesis in primary cultures of adult rat CF. ANG II stimulates collagen production in these cells. Coincubation with agents that elevate cellular cAMP [the ADO agonist, 5'-N-ethylcarboxamidoadensoine (NECA), and forskolin] inhibited the stimulatory effects of ANG II. However, direct stimulators and inhibitors of protein kinase A (PKA) did not alter ANG II-induced collagen synthesis, indicating that PKA does not mediate the inhibitory effects of NECA. Inhibitors of AMP-kinase (AMPK) and extracellular signal-regulated kinase 1/2 (ERK1/2) do not alter NECA-inhibited collagen synthesis. However, activation of exchange factor directly activated by cAMP (Epac) mimicked the effects of NECA on ANG II-stimulated collagen synthesis. Inhibition of phosphoinositol-3 kinase (PI3K) reduced the inhibitory effects of NECA on ANG II-induced collagen synthesis, suggesting that NECA acts via PI3K. Furthermore, inhibition of PI3K also relieved the inhibitory effect of Epac activation on ANG II-stimulated collagen synthesis. Thus it appears that ADO activates the A(2)R-G(s)-adenylyl cyclase pathway and that the resultant cAMP reduces collagen synthesis via a PKA-independent, Epac-dependent pathway that feeds through PI3K.
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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.