title: CB2R orchestrates fibrogenesis through regulation of inflammatory response during the repair of skeletal muscle contusion.
abstract: 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.
authors.affiliation: Department of Forensic Pathology, China Medical University School of Forensic Medicine Shenyang 110122, Liaoning Province, P. R. China.
authors.forename: Miao
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Forensic Pathology, China Medical University School of Forensic Medicine Shenyang 110122, Liaoning Province, P. R. China.
authors.forename: Shu-Kun
authors.initials: SK
authors.lastname: Jiang
authors.affiliation: Department of Forensic Pathology, China Medical University School of Forensic Medicine Shenyang 110122, Liaoning Province, P. R. China.
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Tian
authors.affiliation: Department of Forensic Pathology, China Medical University School of Forensic Medicine Shenyang 110122, Liaoning Province, P. R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Forensic Pathology, China Medical University School of Forensic Medicine Shenyang 110122, Liaoning Province, P. R. China ; Remote Forensic Consultation Center, Collaborative Innovation Center of Judicial Civilization, China University of Political Science and Law Beijing 100192, P. R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Department of Forensic Pathology, China Medical University School of Forensic Medicine Shenyang 110122, Liaoning Province, P. R. China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Wang
authors.affiliation: Department of Forensic Pathology, China Medical University School of Forensic Medicine Shenyang 110122, Liaoning Province, P. R. China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Li
authors.affiliation: Department of Forensic Pathology, China Medical University School of Forensic Medicine Shenyang 110122, Liaoning Province, P. R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Forensic Pathology, China Medical University School of Forensic Medicine Shenyang 110122, Liaoning Province, P. R. China.
authors.forename: Jiao-Yong
authors.initials: JY
authors.lastname: Li
authors.affiliation: Department of Forensic Pathology, China Medical University School of Forensic Medicine Shenyang 110122, Liaoning Province, P. R. China.
authors.forename: Meng-Zhou
authors.initials: MZ
authors.lastname: Zhang
authors.affiliation: Department of Forensic Pathology, China Medical University School of Forensic Medicine Shenyang 110122, Liaoning Province, P. R. China ; Remote Forensic Consultation Center, Collaborative Innovation Center of Judicial Civilization, China University of Political Science and Law Beijing 100192, P. R. China.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Guan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D003288:Contusions / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D008297:Male; D018482:Muscle, Skeletal / Q000293:injuries / Q000473:pathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D015415:Biomarkers; D018925:Chemokines; C469526:Cnr2 protein, rat; D016207:Cytokines; D043885:Receptor, Cannabinoid, CB2
keywords: CB2R; fibrosis; inflammation; skeletal muscle injury; wound repair