title: Adenosine A(2A) receptors promote collagen production by a Fli1- and CTGF-mediated mechanism.
abstract: BACKGROUND
  Adenosine, acting through the A(2A) receptor, promotes tissue matrix production in the skin and the liver and induces the development of dermal fibrosis and cirrhosis in murine models. Since expression of A(2A) receptors is increased in scleroderma fibroblasts, we examined the mechanisms by which the A(2A) receptor produces its fibrogenic effects.
  
  
  METHODS
  The effects of A(2A) receptor ligation on the expression of the transcription factor, Fli1, a constitutive repressor for the synthesis of matrix proteins, such as collagen, is studied in dermal fibroblasts. Fli1 is also known to repress the transcription of CTGF/CCN2, and the effects of A(2A) receptor stimulation on CTGF and TGF-β1 expression are also examined.
  
  
  RESULTS
  A(2A) receptor occupancy suppresses the expression of Fli1 by dermal fibroblasts. A(2A) receptor activation induces the secretion of CTGF by dermal fibroblasts, and neutralization of CTGF abrogates the A(2A) receptor-mediated enhancement of collagen type I production. A(2A)R activation, however, resulted in a decrease in TGF-β1 protein release.
  
  
  CONCLUSIONS
  Our results suggest that Fli1 and CTGF are important mediators of the fibrogenic actions of adenosine and the use of small molecules such as adenosine A(2A) receptor antagonists may be useful in the therapy of dermal fibrosis in diseases such as scleroderma.
authors.forename: Edwin S L
authors.initials: ES
authors.lastname: Chan
authors.forename: Hailing
authors.initials: H
authors.lastname: Liu
authors.forename: Patricia
authors.initials: P
authors.lastname: Fernandez
authors.forename: Alex
authors.initials: A
authors.lastname: Luna
authors.forename: Miguel
authors.initials: M
authors.lastname: Perez-Aso
authors.forename: Andreea M
authors.initials: AM
authors.lastname: Bujor
authors.forename: Maria
authors.initials: M
authors.lastname: Trojanowska
authors.forename: Bruce N
authors.initials: BN
authors.lastname: Cronstein
mesh_terms: D000241:Adenosine / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis*; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051789:Proto-Oncogene Protein c-fli-1 / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012594:Scleroderma, Localized / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000378:metabolism / Q000473:pathology
chemical_list: C526317:CCN2 protein, human; C078433:FLI1 protein, human; D051789:Proto-Oncogene Protein c-fli-1; D043705:Receptor, Adenosine A2A; D055513:Connective Tissue Growth Factor; D003094:Collagen; D000241:Adenosine