Botulinum toxin type A inhibits M1 macrophage polarization by deactivation of JAK2/STAT1 and IκB/NFκB pathway and contributes to scar alleviation in aseptic skin wound healing - 27/04/24
, Zhi-gang Cai a, ⁎, 3 Abstract |
The non-neuronal and non-muscular effects of botulinum toxin type A (BTXA) on scar reduction has been discovered. This study was designed to investigate the effects of BTXA on macrophages polarization during the early stage of skin repair. A skin defect model was established on the dorsal skin of SD rats. BTXA was intracutaneous injected into the edge of wound immediately as the model was established. Histological examinations were performed on scar samples. Raw 264.7 was selected as the cell model of recruited circulating macrophages, and was induced for M1 polarization by LPS. Identify the signaling pathways that primarily regulated M1 polarization and respond to BTXA treatment. Application of BTXA at early stage of injury significantly reduced the scar diameter without delaying wound closure. BTXA treatment improved fiber proliferation and arrangement, and inhibited angiogenesis in scar granular tissue. The number of M1 macrophages and the levels of pro-inflammation were decreased after treated with BTXA in scar tissues. LPS activated JAK2/STAT1 and IκB/NFκB pathways were downregulated by BTXA, as well as LPS induced M1 polarization. At early stage of skin wound healing, injection of BTXA effectively reduced the number of M1 macrophages and the levels of pro-inflammatory mediators which contributes to scar alleviation. BTXA resisted the M1 polarization of macrophages induced by LPS via deactivating the JAK2/STAT1 and IκB/NFκB pathways.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Application of BTXA at the early inflammatory stage of wound healing decreases the scar formation. |
• | BTXA inhibits the M1 polarization of macrophages by regulating JAK2/STAT1 and IκB-α/NFκB pathways. |
• | The study offers a theoretical basis for the optimal timing of clinical preventive use of BTXA to alleviate scar formation. |
Abbreviations : BTXA, DAB, INOS, IL-1β, IL-6, IκB, JAK2, LPS, NFκB, SD, STAT1, TNF-α
Keywords : Botulinum toxin type A, Scar formation, M1 macrophage, Inflammation, Wound healing
Plan
Vol 174
Article 116468- mai 2024 Retour au numéro
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