Pharmacological blockade of adenosine A2A receptors diminishes scarring.

Abstract

Adenosine A2A receptor (A2AR) stimulation promotes wound healing and is required for the development of fibrosis in murine models of scleroderma and cirrhosis. Nonetheless, the role of A2AR in the formation of scars following skin trauma has not been explored. Here, we examined the effect of pharmacological blockade of A2AR, with the selective adenosine A2AR-antagonist ZM241385 (2.5 mg/ml), in a murine model of scarring that mimics human scarring. We found that application of the selective adenosine A2AR antagonist ZM241385 decreased scar size and enhanced the tensile strength of the scar. Within the scar itself, collagen alignment and composition (marked reduction in collagen 3), but not periostin, biglycan, or fibronectin accumulation, was improved by application of ZM241385. Moreover, A2AR blockade reduced the number of myofibroblasts and angiogenesis but not macrophage infiltration in the scar. Taken together, our work strongly suggests that pharmacological A2AR blockade can be used to diminish scarring while improving the collagen composition and tensile strength of the healed wound.

• Authors: Miguel Perez-Aso, Luis Chiriboga, Bruce N Cronstein
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 26 Issue 10 Pg. 4254-63 (Oct 2012) ISSN: 1530-6860 [Electronic] United States
• PMID: 22767233 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adenosine A2 Receptor Antagonists
• Receptor, Adenosine A2A
• Triazines
• Triazoles
• ZM 241385
• Collagen

Topics

• Adenosine A2 Receptor Antagonists (therapeutic use)
• Animals
• Blotting, Western
• Cicatrix (drug therapy, metabolism)
• Collagen (metabolism)
• Immunohistochemistry
• Male
• Mice
• Mice, Inbred C57BL
• Receptor, Adenosine A2A (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Triazines (therapeutic use)
• Triazoles (therapeutic use)
• Wound Healing (drug effects, genetics)