ArticleThe Journal of biological chemistry2013
Hydrolysis of extracellular ATP by ectonucleoside triphosphate diphosphohydrolase (ENTPD) establishes the set point for fibrotic activity of cardiac fibroblasts.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- An innovative in vitro model for studying the biology of cardiac fibroblasts originating from the epicardium.Disease models & mechanisms · 2026Article
- CD39 and CD73: biological functions, diseases and therapy.Molecular biomedicine · 2025Review
- P2 X 7 receptor is a critical regulator of extracellular ATP-induced profibrotic genes expression in rat kidney: implication of transforming growth factor-β/Smad signaling pathway.Purinergic signalling · 2024Article
- Investigation of coagulation and proteomics profiles in symptomatic feline hypertrophic cardiomyopathy and healthy control cats.BMC veterinary research · 2024Article
- Blockage of the adenosine APurinergic signalling · 2024Article
- Interference mechanism of benzo[a]pyrene exposure on the taste substance metabolisms in Ruditapes philippinarum.Environmental science and pollution research international · 2024Article
- The role of intercellular communication in diabetic nephropathy.Frontiers in immunology · 2024Review
- The Pleiotropic Role of Extracellular ATP in Myocardial Remodelling.Molecules (Basel, Switzerland) · 2023Review
- Ectonucleoside triphosphate diphosphohydrolase-1 (CD39) impacts TGF-β1 responses: insights into cardiac fibrosis and function following myocardial infarction.American journal of physiology. Heart and circulatory physiology · 2022Article
- Adenosine and Adenosine Receptors: Advances in Atrial Fibrillation.Biomedicines · 2022Review
- P2Y2 promotes fibroblasts activation and skeletal muscle fibrosis through AKT, ERK, and PKC.BMC musculoskeletal disorders · 2021Article
- Danegaptide Prevents TGFβ1-Induced Damage in Human Proximal Tubule Epithelial Cells of the Kidney.International journal of molecular sciences · 2021Article
- Blocking Connexin-43 mediated hemichannel activity protects against early tubular injury in experimental chronic kidney disease.Cell communication and signaling : CCS · 2020Article
- Inhibition of P2X7 Purinergic Receptor Ameliorates Cardiac Fibrosis by Suppressing NLRP3/IL-1Oxidative medicine and cellular longevity · 2020Article
- Kinetics of MSC-based enzyme therapy for immunoregulation.Journal of translational medicine · 2019Article
- Cell-subtype-specific changes in adenosine pathways in schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- N6-(2-Hydroxyethyl) Adenosine FromFrontiers in physiology · 2018Article
- Acute In Vivo Analysis of ATP Release in Rat Kidneys in Response to Changes of Renal Perfusion Pressure.Journal of the American Heart Association · 2017Article
- Adenosine AThe American journal of pathology · 2017Article
- Ectonucleotidase CD39-driven control of postinfarction myocardial repair and rupture.JCI insight · 2017Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The establishment of set points for cellular activities is essential in regulating homeostasis. Here, we demonstrate key determinants of the fibrogenic set point of cardiac fibroblasts (CFs) by focusing on the pro-fibrotic activity of ATP, which is released by CFs. We tested the hypothesis that the hydrolysis of extracellular ATP by ectonucleoside triphosphate diphosphohydrolases (ENTPDs) regulates pro-fibrotic nucleotide signaling. We detected two ENTPD isoforms, ENTPD-1 and -2, in adult rat ventricular CFs. Partial knockdown of ENTPD-1 and -2 with siRNA increased basal extracellular ATP concentration and enhanced the pro-fibrotic effect of ATP stimulation. Sodium polyoxotungstate-1, an ENTPD inhibitor, not only enhanced the pro-fibrotic effects of exogenously added ATP but also increased basal expression of α-smooth muscle actin, plasminogen activator inhibitor-1 and transforming growth factor (TGF)-β, collagen synthesis, and gel contraction. Furthermore, we found that adenosine, a product of ATP hydrolysis by ENTPD, acts via A2B receptors to counterbalance the pro-fibrotic response to ATP. Removal of extracellular adenosine or inhibition of A2B receptors enhanced pro-fibrotic ATP signaling. Together, these results demonstrate the contribution of basally released ATP in establishing the set point for fibrotic activity in adult rat CFs and identify a key role for the modulation of this activity by hydrolysis of released ATP by ENTPDs. These findings also imply that cellular homeostasis and fibrotic response involve the integration of signaling that is pro-fibrotic by ATP and anti-fibrotic by adenosine and that is regulated by ENTPDs.
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