title: Cannabinoid CB₂ receptors are involved in the regulation of fibrogenesis during skin wound repair in mice.
abstract: Studies have shown that cannabinoid CB2 receptors are involved in wound repair, however, its physiological roles in fibrogenesis remain to be elucidated. In the present study, the capacity of cannabinoid CB2 receptors in the regulation of skin fibrogenesis during skin wound healing was investigated. To assess the function of cannabinoid CB2 receptors, skin excisional BALB/c mice were treated with either the cannabinoid CB2 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 CB2 receptors modulate fibrogenesis and the TGF‑β/Smad profibrotic signaling pathway during skin wound repair in the mouse.
authors.affiliation: Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Li
authors.affiliation: Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Wang
authors.affiliation: Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Shu-Kun
authors.initials: SK
authors.lastname: Jiang
authors.affiliation: Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Miao
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Tian
authors.affiliation: Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Jiao-Yong
authors.initials: JY
authors.lastname: Li
authors.affiliation: Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Guan
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D012871:Skin Diseases / Q000378:metabolism / Q000473:pathology*; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: C558396:Acta2 protein, mouse; D000199:Actins; D024042:Collagen Type I; D024061:Collagen Type III; D016207:Cytokines; D007211:Indoles; D043885:Receptor, Cannabinoid, CB2; D018125:Receptors, Transforming Growth Factor beta; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C094023:iodopravadoline