Purinergic signaling in scarring

Davide Ferrari, Roberto Gambari, Marco Idzko, Tobias Müller, Cristina Albanesi, Saveria Pastore, Gaetano La Manna, Simon C. Robson, Bruce Cronsteink

Research output: Contribution to journalReview article

Abstract

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.

Original languageEnglish
Pages (from-to)3-12
Number of pages10
JournalFASEB Journal
Volume30
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

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Keywords

  • Adenosine
  • COPD
  • Crohn's disease
  • Extracellular nucleotides
  • Fibrosis

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Ferrari, D., Gambari, R., Idzko, M., Müller, T., Albanesi, C., Pastore, S., La Manna, G., Robson, S. C., & Cronsteink, B. (2016). Purinergic signaling in scarring. FASEB Journal, 30(1), 3-12. https://doi.org/10.1096/fj.15-274563