转化生长因子β/Smad信号通路与瘢痕疙瘩的靶向治疗  

Transforming growth factor beta/Smad signaling pathway and targeted therapy of keloid scars

作　　者：姚思琦 黎文正 汪虹[1] Yao Siqi;Li Wenzheng;Wang Hong(Department of Burn Surgery,The Second Affiliated Hospital of Kunming Medical University,Kunming 650101,Yunnan Province,China)

机构地区：[1]昆明医科大学第二附属医院烧伤外科,云南省昆明市650101

出　　处：《中国组织工程研究》2024年第16期2619-2624,共6页Chinese Journal of Tissue Engineering Research

基　　金：云南省“高层次人才培养支持计划项目”(YNWR-MY-2020-047),项目负责人:汪虹;昆明医科大学研究生创新基金项目(2023S326),项目负责人:姚思琦。

摘　　要：背景:关于瘢痕疙瘩的发病机制目前尚不完全清楚。近年来瘢痕疙瘩涉及的发病机制有一些新的研究进展,包括转化生长因子β(transforming growth factor-β,TGF-β)/Smad信号通路、缺血缺氧、缺氧诱导因子1(HIF-1)、丝裂原活化蛋白激酶(MAPK)通路等。TGF-β/Smad通路目前研究较为清晰,TGF-β/Smad通路的激活促进瘢痕疙瘩的发展。目的:对TGF-β/Smad信号通路进行综述并评估以该通路为靶点的主要治疗策略,以期有助于临床拓展更有效的治疗方式。方法:用计算机检索PubMed、Web of Science数据库等英文数据库及中国知网、万方数据知识服务平台等中文数据库,检索从2017年1月至2023年4月发表的文献,英文检索词为“Keloid,Fibroblasts,TGF-β/Smad,Extracellular Matrix,Collagen,Treatment Measures”,中文检索词为“瘢痕疙瘩,成纤维细胞,转化生长因子β/Smad,细胞外基质,胶原,治疗措施”。根据纳入和排除标准最终纳入72篇文献进行结果分析。结果与结论:①总结了TGF-β/Smad信号通路在瘢痕疙瘩发生发展中的作用机制:TGF-β1和TGF-β2在瘢痕疙瘩中呈现过表达状态,而TGF-β3表现出抗纤维化作用;Smad2/3与Smad1/5/8同Smad4结合形成复合物进入细胞核发挥纤维化作用,而Smad6/7呈现抑制瘢痕疙瘩增生的作用;②TGF-β/Smad通路目前在瘢痕疙瘩中的研究最为清晰,列举了多条通过靶向抑制该通路激活的途径,可较大程度达到抑制瘢痕疙瘩发生发展的目的;③瘢痕疙瘩目前还未有单一的临床金标准治疗方式,单靠抑制TGF-β/Smad通路还不能完全抑制瘢痕疙瘩的发展,还需要综合考虑全身各个系统之间同瘢痕疙瘩的联系。尽管已经在纤维化级联反应中发现了很多有希望的靶点,但在临床中还需要更多研究来转化为靶向治疗。BACKGROUND:There are many studies focusing on keloid scars,but the pathogenesis is not fully understood.In recent years,there have been some new research advances in the pathogenesis of keloids,including transforming growth factor-β(TGF-β)/Smad signaling pathway,ischemic hypoxia,hypoxia-inducible factor 1(HIF-1),and mitogen-activated protein kinase(MAPK)pathway.The TGF-β/Smad pathway is now more clearly studied,and activation of the TGF-β/OBJECTIVE:To review the TGF-β/Smad signaling pathway and evaluate the main therapeutic strategies targeting this pathway,with the aim of contributing to the development of more effective clinical treatments.METHODS:PubMed and Web of Science,CNKI and WanFang databases were searched by computer for relevant literature published from January 2017 to April 2023 with the search terms of“keloid,fibroblasts,TGF-β/Smad,extracellular matrix,collagen,treatment measures”in English and Chinese.Seventy-two articles were finally included according to the inclusion and exclusion criteria.RESULTS AND CONCLUSION:The mechanism of TGF-β/Smad signaling pathway in the occurrence and development of keloids is summarized:TGF-β1 and TGF-β2 are overexpressed in keloids,while TGF-β3 shows antifibrotic effects.Smad2/3 and Smad1/5/8 are combined with Smad4 to form a complex that enters the nucleus and plays a fibrotic role,while Smad6/7 can inhibit keloid hyperplasia.The TGF-β/Smad signaling pathway is currently the most clearly studied pathway in keloids,and there are many pathways targeted to inhibit the activation of this pathway,which can inhibit the occurrence and development of keloids to a greater extent.Currently,there is no single clinical gold standard treatment for keloids,and inhibition of the TGF-β/Smad pathway alone cannot completely inhibit the development of keloids.A comprehensive consideration of the association between all systemic systems and keloids is needed.Although many promising targets have been identified in the fibrosis cascade,more research is needed to translat

关 键 词：瘢痕疙瘩 成纤维细胞 TGF-Β/SMAD 细胞外基质 胶原蛋白 治疗措施 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R751