Blocking adenosine A2A receptor reduces peritoneal fibrosis in two independent experimental models

Nakav, Sigal; Kachko, Leonid; Vorobiov, Marina; Rogachev, Boris; Chaimovitz, Cidio; Zlotnik, Moshe; Douvdevani, Amos

doi:10.1093/ndt/gfp041

Cited by 17 publications

(11 citation statements)

References 28 publications

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“…This latter finding might account for the well-documented observation that coffee drinking and caffeine ingestion reduces deaths from liver disease 145-149 . Peritoneal fibrosis also depends on A 2a stimulation in animal models 150 . In the setting of priapism, in which the chronically engorged penis becomes hypoxic, adenosine release leads to both vasodilation and fibrosis via activation of A 2b 151,152 .…”

Section: Adenosine Receptors and Fibrosismentioning

confidence: 99%

Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases

Cronstein¹,

2016

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Adenosine, a nucleoside derived primarily from the extracellular hydrolysis of adenine nucleotides, is a potent regulator of inflammation. Adenosine mediates its effects on inflammatory cells by engaging one or more cell-surface receptors. The expression and function of adenosine receptors on different cell types change during the course of rheumatic diseases, such as rheumatoid arthritis. Targeting adenosine receptors directly for the treatment of rheumatic diseases is currently under study; however, indirect targeting of adenosine receptors by enhancing adenosine levels at inflamed sites accounts for most of the anti-inflammatory effects of methotrexate, the anchor drug for the treatment of rheumatoid arthritis. In this Review, we discuss the regulation of extracellular adenosine levels and the role of adenosine in regulating the inflammatory and immune responses in rheumatic diseases such as Rheumatoid Arthritis, psoriasis and other types of inflammatory arthritis. In addition, adenosine and its receptors are involved in promoting fibrous matrix production in the skin and other organs and the role of adenosine in fibrosis and fibrosing diseases will also be discussed.

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Section: Adenosine Receptors and Fibrosismentioning

confidence: 99%

Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases

Cronstein¹,

2016

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“…Peritoneal fibrosis is a common complication of chronic peritoneal dialysis or surgery and may lead to diminished efficacy of peritoneal dialysis, development of intestinal adhesions, and obstruction. Recent work indicates that either pharmacological blockade or deletion of ADO A 2A receptors can diminish peritoneal fibrosis (109). In contrast, others have reported that topical application of ADO and phosphorylated ADO derivatives could, by acting via ADO receptors, diminish peritoneal adhesions in a rodent model (110).…”

Section: Modulation Of Peritoneal and Cardiac Fibrosis By Adomentioning

confidence: 99%

Purinergic signaling in scarring

et al. 2015

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Adenosine (ADO) and nucleotides such as ATP, ADP, and uridine 5'-triphosphate (UTP), among others, may serve as extracellular signaling molecules. These mediators activate specific cell-surface receptors-namely, purinergic 1 and 2 (P1 and P2)-to modulate crucial pathophysiological responses. Regulation of this process is maintained by nucleoside and nucleotide transporters, as well as the ectonucleotidases ectonucleoside triphosphate diphosphohydrolase [ENTPD; cluster of differentiation (CD)39] and ecto-5'-nucleotidase (5'-NT; CD73), among others. Cells involved in tissue repair, healing, and scarring respond to both ADO and ATP. Our recent investigations have shown that modulation of purinergic signaling regulates matrix deposition during tissue repair and fibrosis in several organs. Cells release adenine nucleotides into the extracellular space, where these mediators are converted by CD39 and CD73 into ADO, which is anti-inflammatory in the short term but may also promote dermal, heart, liver, and lung fibrosis with repetitive signaling under defined circumstances. Extracellular ATP stimulates cardiac fibroblast proliferation, lung inflammation, and fibrosis. P2Y2 (UTP/ATP) and P2Y6 [ADP/UTP/uridine 5'-diphosphate (UDP)] have been shown to have profibrotic effects, as well. Modulation of purinergic signaling represents a novel approach to preventing or diminishing fibrosis. We provide an overview of the current understanding of purinergic signaling in scarring and discuss its potential to prevent or decrease fibrosis.-Ferrari, D., Gambari, R., Idzko, M., Müller, T., Albanesi, C., Pastore, S., La Manna, G., Robson, S. C., Cronstein, B. Purinergic signaling in scarring

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“…These results also parallel those findings of murine models of cirrhosis and peritoneal fibrosis in which adenosine A 2A receptor antagonism also has been observed to be beneficial. 23,31 TGF-β is cytokine produced and released by platelets, fibroblasts, and endothelial, epithelial, and inflammatory cells, such as macrophages and lymphocytes, after a wound occurs. TGF-β participates in the regulatory process of cell proliferation, with an important role in tissue repair, and has been linked to the formation of hypertrophic scars and keloids in a number of ways.…”

Section: Discussionmentioning

confidence: 99%

Absence of the Adenosine A2A Receptor Attenuates Hypertrophic Scarring in Mice

Huo

Wang

et al. 2013

Journal of Burn Care & Research

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Hypertrophic scar following cutaneous wounding is the result of the body overproducing collagen, and it has been shown that the activation of the adenosine A(2A) receptor promotes tissue repair, wound healing, and extracellular matrix production. In this study, we explored the role of adenosine receptor in hypertrophic scarring in adenosine A(2A) receptor knockout mice models. Mechanical stress was applied to a healing wound to produce hypertrophic scars in adenosine A(2A) receptor knockout mice and wild-type controls. Total scar areas were evaluated after routine hematoxylin and eosin and picrosirius red staining and hydroxyproline content measured colorimetrically. Expression of transforming growth factor-β in scar tissues was measured using the Western blotting method. Compared with the wild-type control group, adenosine A(2A) receptor knockout mice showed significantly less thickness, smaller cross-sectional area, and significantly lower hydroxyproline levels and transforming growth factor-β levels. These results demonstrate that adenosine A(2A) receptors play an active role in the pathogenesis of dermal fibrosis and suggest a novel therapeutic target in the prevention and treatment of hypertrophic scarring.

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Blocking adenosine A2A receptor reduces peritoneal fibrosis in two independent experimental models

Abstract: Our data suggest that adenosine through its A(2A)R promotes peritoneal fibrosis and therefore should be considered as a target for pharmacological intervention.

Cited by 17 publications

References 28 publications

Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases

Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases

Purinergic signaling in scarring

Absence of the Adenosine A2A Receptor Attenuates Hypertrophic Scarring in Mice

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