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Fucosyltransferase 9 promotes neuronal differentiation and functional recovery after spinal cord injury by suppressing the activation of Notch signaling

查看全文 作　　者：Jiewen [1]Chen;Xiaolin [1]Zeng;Wenwu [1]Zhang;Gang [1]Li;Haoming [2]Zhong;Chengzhong [2]Xu;Xiang [1]Li;Tao [2]Lin 高影响力作者 机构地区：[1]Department of Spine Surgery,The First Affiliated Hospital,Sun Yat-sen University,Guangzhou 510080,China;[2]Department of Orthopedics and Traumatology,Zhujiang Hospital,Southern Medical University,Guangzhou 510280,China高影响力机构 出　　处：《Acta Biochimica et Biophysica Sinica》索引2023年第55卷第10期,共11页高影响力期刊 基　　金：supported by the grants from the Guangdong Basic and Applied Basic Research Foundation(No.2019A1515110923 to T.L.);the National Natural Science Foundation of China(No.82102528 to X.L.);the Natural Science Foundation of Guangdong Province,China(Nos.2021A1515010358 and 2020A1515110679 to X.L.). 摘　　要：Individuals with spinal cord injury(SCI)suffer from permanent disabilities such as severe motor,sensory and autonomic dysfunction.Neural stem cell transplantation has proven to be a potential strategy to promote regeneration of the spinal cord,since NSCs can produce neurotrophic growth factors and differentiate into mature neurons to reconstruct the injured site.However,it is necessary to optimize the differentiation of NSCs before transplantation to achieve a better regenerative outcome.Inhibition of Notch signaling leads to a transition from NSCs to neurons,while the underlying mechanism remains inadequately understood.Our results demonstrate that overexpression of fucosyltransferase 9(Fut9),which is upregulated by Wnt4,promotes neuronal differentiation by suppressing the activation of Notch signaling through disruption of furin-like enzyme activity during S1 cleavage.In an in vivo study,Fut9-modified NSCs efficiently differentiates into neurons to promote functional and histological recovery after SCI.Our research provides insight into the mechanisms of Notch signaling and a potential treatment strategy for SCI. 关 键 词：neural stem cells neuronal differentiation neural stem cell transplantation NOTCH WNT FUCOSYLTRANSFERASE
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