Nerve bundle formation during the promotion of peripheral nerve regeneration:collagenⅥ-neural cell adhesion molecule 1 interaction |
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作者姓名: | Jia-Hui Sun Ming Huang Zhou Fang Tian-Xiao Li Ting-Ting Wu Yi Chen Da-Ping Quan Ying-Ying Xu Yu-Ming Wang Yi Yang Jian-Long Zou |
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作者单位: | Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University;Key Laboratory of Neurological Function and Health;Zhongshan School of Medicine;Department of Pharmacy;Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education;Department of Orthopedic Trauma and Microsurgery |
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基金项目: | supported by the National Natural Science Foundation of China,No.31800892(to JLZ);the Natural Science Foundation of Guangdong Province of China,No.2018A030310254(to YY);a grant from Guangzhou Medical University Start-up Project of China,No.B195002002048(to JLZ)。 |
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摘 要: | The formation of nerve bundles,which is partially regulated by neural cell adhesion molecule 1(NCAM1),is important for neural network organization during peripheral nerve regeneration.However,little is known about how the extracellular matrix(ECM)microenvironment affects this process.Here,we seeded dorsal root ganglion tissue blocks on different ECM substrates of peripheral nerve ECM-derived matrixgel,Matrigel,laminin 521,collagen I,and collagen IV,and observed well-aligned axon bundles growing in the peripheral nerve ECM-derived environment.We confirmed that NCAM1 is necessary but not sufficient to trigger this phenomenon.A protein interaction assay identified collagen VI as an extracellular partner of NCAM1 in the regulation of axonal fasciculation.Collagen VI interacted with NCAM1 by directly binding to the FNIII domain,thereby increasing the stability of NCAM1 at the axolemma.Our in vivo experiments on a rat sciatic nerve defect model also demonstrated orderly nerve bundle regeneration with improved projection accuracy and functional recovery after treatment with 10 mg/m L Matrigel and 20μg/m L collagen VI.These findings suggest that the collagen VI-NCAM1 pathway plays a regulatory role in nerve bundle formation.This study was approved by the Animal Ethics Committee of Guangzhou Medical University(approval No.GY2019048)on April 30,2019.
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关 键 词: | axonal fasciculation collagen VI extracellular matrix MICROENVIRONMENT nerve bundle formation nerve projection neural cell adhesion molecule 1 NEUROGENESIS peripheral nerve regeneration |
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