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

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...

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Main Authors: Yan-ping Zou, Xiao-feng Shan, Jia-xuan Qiu, Lin-na Wang, Ruo-lan Xiang, Zhi-gang Cai
Format: Article
Language:English
Published: Elsevier 2024-05-01
Series:Biomedicine & Pharmacotherapy
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0753332224003524
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author Yan-ping Zou
Xiao-feng Shan
Jia-xuan Qiu
Lin-na Wang
Ruo-lan Xiang
Zhi-gang Cai
author_facet Yan-ping Zou
Xiao-feng Shan
Jia-xuan Qiu
Lin-na Wang
Ruo-lan Xiang
Zhi-gang Cai
author_sort Yan-ping Zou
collection DOAJ
description 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.
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spelling doaj.art-1af3d496f1854660914d8c94aa9448ca2024-03-22T05:38:45ZengElsevierBiomedicine & Pharmacotherapy0753-33222024-05-01174116468Botulinum 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 healingYan-ping Zou0Xiao-feng Shan1Jia-xuan Qiu2Lin-na Wang3Ruo-lan Xiang4Zhi-gang Cai5Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, Beijing, ChinaDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, Beijing, ChinaDepartment of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, ChinaLanzhou Biotechnique Development Co., Ltd, Lanzhou, Gansu, ChinaDepartment of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, China; Correspondence to: Peking University School of Basic Medical Sciences, No. 38 Xueyuan Road, Haidian District, Beijing, 100191, P.R. China.Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, Beijing, China; Correspondence to: No.22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, P.R. China.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.http://www.sciencedirect.com/science/article/pii/S0753332224003524Botulinum toxin type AScar formationM1 macrophageInflammationWound healing
spellingShingle Yan-ping Zou
Xiao-feng Shan
Jia-xuan Qiu
Lin-na Wang
Ruo-lan Xiang
Zhi-gang Cai
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
Biomedicine & Pharmacotherapy
Botulinum toxin type A
Scar formation
M1 macrophage
Inflammation
Wound healing
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Botulinum toxin type A
Scar formation
M1 macrophage
Inflammation
Wound healing
url http://www.sciencedirect.com/science/article/pii/S0753332224003524
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