Cannabinoid CB(2) receptors are involved in the regulation of fibrogenesis during skin wound repair in mice

Studies have shown that cannabinoid CB(2) receptors are involved in wound repair, however, its physiological roles in fibrogenesis remain to be elucidated. In the present study, the capacity of cannabinoid CB(2) receptors in the regulation of skin fibrogenesis during skin wound healing was investigated. To assess the function of cannabinoid CB(2) receptors, skin excisional BALB/c mice were treated either the cannabinoid CB(2) receptor selective agonist, GP1a, or antagonist, AM630. Skin fibrosis was assessed by histological analysis and profibrotic cytokines were determined by immunohistochemistry, immunofluorescence staining, reverse transcription-quantitative polymerase chain reaction and immunoblotting in these animals. GP1a decreased collagen deposition, reduced the levels of transforming growth factor (TGF)-β1, TGF-β receptor I (TβRI) and phosphorylated small mothers against decapentaplegic homolog 3 (P-Smad3), but elevated the expression of its inhibitor, Smad7. By contrast, AM630 increased collagen deposition and the expression levels of TGF-β1, TβRI and P-Smad3. These results indicated that cannabinoid CB(2) receptors modulate fibrogenesis and the TGF-β/Smad profibrotic signaling pathway during skin wound repair in the mouse.