CB2R orchestrates fibrogenesis through regulation of inflammatory response during the repair of skeletal muscle contusion

摘要

Skeletal muscle injuries repair typically is an overlapping event between inflammation and tissue repair. Our previous study has demonstrated that activation of cannabinoid receptor type 2 (CB2R) by JWH-133 alleviates fibrosis in the repair of rat skeletal muscle contusion. Meanwhile, accumulated data show that CB2R stimulation exerts anti-inflammatory property in sepsis and cystitis. However, the effects of CB2R on inflammatory cytokines in response to the repair of skeletal muscle contusion are still unknown. In this study, we used selective agonist or antagonist of CB2R to observe the role of CB2R on inflammation and fibrogenesis during the repair of contused skeletal muscles in rats. Our results revealed that treatment with Gp1a, a selective CB2R agonist, significantly decreased the infiltration of neutrophils and macrophages, the expression of pro-inflammatory cytokines MCP-1, TNF-α, IL-1β and IL-6, the expression of pro-fibrotic cytokines IL-4, IL-13, TGF-β and P-Smad3 while increased anti-fibrotic cytokine IL-10 production as compared with Vehicle. The opposite results were observed in the CB2R inhibition group with AM630. Our study demonstrated that CB2R orchestrates fibrogenesis through regulation of inflammatory response during the repair of skeletal muscle contusion.