摘要
背景:近年来研究显示,Hippo信号通路与脊髓损伤之后的病理变化密切相关,通过对该信号通路的针对性靶向调控,可以为临床脊髓损伤的治疗提供新的思路。目的:对Hippo信号通路在脊髓损伤中调控机制的研究进展做一综述。方法:由第一作者检索PubMed、Web of Science数据库相关文献,以“spinal cord injury,nervous system,Hippo signaling pathway,MST1/2,LATS1/2,MOB1A/B,NDR1/2,YAP,TAZ,neurite,axonal regeneration,myelination,neuronal death,inflammation,glial scar,gliosis”为检索词,检索时限为2007年9月至2022年2月,排除与研究目的不相关及重复性研究文章,纳入符合标准的62篇文献进行综述。结果与结论:Hippo信号通路分子在神经细胞中广泛高表达,YAP调控中枢神经发育,并且维持着神经细胞增殖、分化的动态平衡。在继发性脊髓损伤的病理机制中,Hippo通路发挥其调控作用:①NDR、MOB1以及YAP分子均可以促进神经突的生长;②YAP/TAZ对于髓鞘的合成以及髓鞘生长动态调控方面有重要作用;③通过抑制Hippo通路的表达可以减轻神经元凋亡和神经功能缺损;④胶质细胞和成纤维细胞均能被YAP调控而影响胶质瘢痕的形成。大量研究表明,调控Hippo通路为脊髓损伤的分子靶向治疗、生物材料的开发提供了新的思路和治疗策略。
BACKGROUND:Recent studies have shown that Hippo signaling pathway is closely related to pathological changes after spinal cord injury.Through targeted regulation of this signaling pathway,it can provide new ideas for the treatment of spinal cord injury in clinical practice.OBJECTIVE:To review the research progress of regulatory mechanism of Hippo signaling pathway in spinal cord injury.METHODS:PubMed and Web of Science databases were searched by the first author.Search terms were“spinal cord injury,nervous system,Hippo signaling pathway,MST1/2,LATS1/2,MOB1A/B,NDR1/2,YAP,TAZ,neurite,axonal regeneration,myelination,neuronal death,inflammation,glial scar,gliosis”.The search time limit was from September 2007 to February 2022.The articles unrelated to the purpose of this study and repeatability were excluded.Finally,62 articles that met the criteria were included for review.RESULTS AND CONCLUSION:Hippo signaling pathway molecules are widely expressed in neuronal cells and YAP regulates central neural development and maintains a dynamic balance of neuronal proliferation and differentiation.In the pathological mechanism of secondary spinal cord injury,the Hippo pathway plays a regulatory role:(1)NDR,MOB1 and YAP molecules can promote the growth of neuropil.(2)YAP/TAZ has an important role in the synthesis of myelin and the dynamic regulation of myelin growth.(3)Inhibition of Hippo pathway expression can reduce neuronal apoptosis and neurological deficits.(4)Both glial cells and fibroblasts can be modulated by YAP to influence glial scar formation.Numerous studies have shown that regulation of Hippo pathway provides new ideas and therapeutic strategies for molecular targeting therapy and development of biomaterials for spinal cord injury.
作者
陶新
徐逸
宋志文
刘锦波
Tao Xin;Xu Yi;Song Zhiwen;Liu Jinbo(The Third Affiliated Hospital of Soochow University,Changzhou 213003,Jiangsu Province,China;Department of Orthopedics,People’s Hospital of Liyang,Changzhou 213300,Jiangsu Province,China)
出处
《中国组织工程研究》
CAS
北大核心
2023年第4期619-625,共7页
Chinese Journal of Tissue Engineering Research
基金
国家自然科学基金面上项目(81972048),项目负责人:刘锦波
国家自然科学基金青年基金项目(81901247),项目负责人:宋志文。
