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Purinergic signaling in scarring
Author(s) -
Ferrari Davide,
Gambari Roberto,
Idzko Marco,
Müller Tobias,
Albanesi Cristina,
Pastore Saveria,
La Manna Gaetano,
Robson Simon C.,
Cronstein Bruce
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.15-274563
Subject(s) - purinergic receptor , purinergic signalling , apyrase , microbiology and biotechnology , extracellular , uridine triphosphate , p2y receptor , adenosine , p2 receptor , fibrosis , cell signaling , adenosine triphosphate , signal transduction , adenine nucleotide , biology , nucleoside triphosphate , extracellular matrix , biochemistry , receptor , adenosine receptor , nucleotide , medicine , gene , agonist
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. P2Y 2 (UTP/ATP) and P2Y 6 [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. FASEB J. 30, 3‐12 (2016). www.fasebj.org