Pharmacological activation of cannabinoid 2 receptor attenuates inflammation, fibrogenesis, and promotes re-epithelialization during skin wound healing
| Autor: | Chang-Sheng Liu, Rui Zhao, Meng Wang, Shu-Kun Jiang, Lin-Lin Wang, Da-Wei Guan, Meng-Zhou Zhang, Jiao-Yong Li, Wen-Wen Dong, Zhi-Ling Tian, Min Liu, Shan-Shan Li, Miao Zhang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Indoles Inflammation Cell Line Receptor Cannabinoid CB2 03 medical and health sciences Mice 0302 clinical medicine Re-Epithelialization medicine Cannabinoid receptor type 2 Animals Humans Epithelial–mesenchymal transition Keratinocyte migration Fibroblast Skin Pharmacology integumentary system Chemistry Fibrosis HaCaT 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Indenes 030220 oncology & carcinogenesis Immunology Cancer research Pyrazoles lipids (amino acids peptides and proteins) Collagen medicine.symptom Keratinocyte Wound healing |
| Zdroj: | European journal of pharmacology. 786 |
| ISSN: | 1879-0712 |
| Popis: | Previous studies showed that cannabinoid 2 (CB2) receptor is expressed in multiple effector cells during skin wound healing. Meanwhile, its functional involvement in inflammation, fibrosis, and cell proliferation in other organs and skin diseases implied CB2 receptor might also regulate skin wound healing. To verify this hypothesis, mice excisional wounds were created and treated with highly selective CB2 receptor agonist GP1a (1-(2,4-dichlorophenyl)-6-methyl- N-piperidin-1-yl-4H-indeno[1,2-c]pyrazole-3-carboxamide) and antagonist AM630 ([6-iodo-2- methyl-1-(2-morpholin-4-ylethyl)indol-3-yl]-(4-methoxyphenyl)methanone) respectively. The inflammatory infiltration, cytokine expression, fibrogenesis, and wound re-epithelialization were analyzed. After CB2 receptor activation, neutrophil and macrophage infiltrations were reduced, and expressions of monocyte chemotactic protein (MCP)-1, stromal cell-derived factor (SDF)-1, Interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF)-A were decreased. Keratinocyte proliferation and migration were enhanced. Wound re-epithelialization was accelerated. Fibroblast accumulation and fibroblast-to-myofibroblast transformation were attenuated, and expression of pro-collagen I was decreased. Furthermore, HaCaT cells in vitro were treated with GP1a or AM630, which revealed that CB2 receptor activation promoted keratinocyte migration by inducing the epithelial to mesenchymal transition. These results, taken together, indicate that activating CB2 receptor could ameliorate wound healing by reducing inflammation, accelerating re-epithelialization, and attenuating scar formation. Thus, CB2 receptor agonist might be a novel perspective for skin wound therapy. |
| Databáze: | OpenAIRE |
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