中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (4): 1607-1620.doi: 10.4103/NRR.NRR-D-24-00232

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

驱动蛋白在神经再生中具有双重功能：损伤诱导KIF4神经表达及在许旺细胞增殖中的作用

  

  • 出版日期:2026-04-15 发布日期:2025-07-28

Injury-induced KIF4A neural expression and its role in Schwann cell proliferation suggest a dual function for this kinesin in neural regeneration

Patrícia D. Correia1, 2, 3, Bárbara M. de Sousa1, 3, Jesús Chato-Astrain1, 3, 4, Joana Paes de Faria5, 6, Veronica Estrada2 , João B. Relvas5, 6, Hans W. Müller2 , Víctor Carriel3, 4, Frank Bosse2, #, Sandra I. Vieira1, *, #   

  1. 1 Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal;  2 Molecular Neurobiology Laboratory, Department of Neurology, UniversityHospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany;  3 Department of Histology & Tissue Engineering Group, University of Granada, Granada, Spain;  4 Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain;  5 Glial Cell Biology Laboratory, Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Porto, Portugal;  6 Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal
  • Online:2026-04-15 Published:2025-07-28
  • Contact: Sandra I. Vieira, PhD, sivieira@ua.pt.
  • Supported by:
    This work was supported by the Portuguese Foundation for Science and Technology (FCT), Centro 2020 and Portugal2020 and the EU FEDER program, via the project GoBack to SIV (PTDC/CVT-CVT/32261/2017; CENTRO-01-0145-FEDER-032261); the doctoral grants of PDC (SFRH/BD/139974/2018) and BMS (2020.06525.BD and DOI 10.54499/2020.06525. BD); the post-doctoral grant to JPF (SFRH/BPD/113359/2015 - program-contract described in paragraphs 4, 5, and 6 of art. 23 of Law no. 1001 57/ 2016, of August 29, as amended by Law no. 57/2017 of July 2019); the project PTDC/MED-NEU/1677/2021 to JBR; the Institute of Biomedicine iBiMED (UIDB/04501/2020 and DOI 10.54499/UIDB/04501/2020; UIDP/04501/2020 and DOI 10.54499/UIDP/04501/2020) and its LiM Bioimaging Facility – a PPBI node (POCI-01-0145-FEDER-022122). The work was also supported by the Research Commission of the Medical Faculty of the Heinrich-Heine-University (HHU) Düsseldorf, and of the Biologisch-Medizinisches Forschungszentrum (BMFZ) of HHU. The study was additionally financed by the Spanish “Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, Ministerio de Economía y Competitividad (Instituto de Salud Carlos III)”, co-financed by the European Union (FEDER program), (grant FIS PI20/00318 and FIS P23/00337 to VC); and grant CPP2021-009070 to VC by the “Proyectos de colaboración público-privada, Plan de Investigación Científica, Técnica y de innovación 2021-2023, Ministerio de Ciencia e Innovación, Unión Europea, Agencia Estatal de Investigación, España”.

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摘要：

与成人中枢神经系统不同，周围神经系统具有内在的再生能力，这种能力依赖于再生相关基因的表达，如某些驱动蛋白家族成员。驱动蛋白通过将特定货物，如蛋白质和膜成分，从细胞体向轴突外围运输，促进神经再生。实验显示，先前被认为仅在发育期间表达的KIF4A也在成年脊椎动物神经系统中表达，并在受伤的周围神经系统细胞中上调。在受伤神经元的细胞体和再生轴突中都能检测到KIF4A，这与其作为轴突运输货物如β1-整合蛋白和L1CAM的功能一致。实验进一步显示，在受伤远端神经残端的许旺细胞中，Kif4a水平显著增加，特别是在它们被重新编程为必需的增殖修复表型时。此外，与非增殖性许旺细胞相比，增殖性培养的许旺细胞中Kif4a mRNA水平大约高出6倍。通过Kif4a敲低进一步证实了Kif4a在许旺细胞增殖中的假定功能，因为这显著减少了体外许旺细胞的增殖。结果表明，KIF4A在成年脊椎动物神经系统中表达，并在周围损伤后上调。KIF4A上调的时机、在再生期间的位置以及其增殖作用，都表明这种蛋白在神经再生中具有双重作用。

https://orcid.org/0000-0003-1053-1107 (Sandra I. Vieira)

关键词: 轴突再生, KIF4驱动蛋白, 神经组织再生, 神经再生, 周围神经损伤, 修复, 许旺细胞

Abstract: Contrary to the adult central nervous system, the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes, such as some kinesin family members. Kinesins contribute to nerve regeneration through the transport of specific cargo, such as proteins and membrane components, from the cell body towards the axon periphery. We show here that KIF4A, associated with neurodevelopmental disorders and previously believed to be only expressed during development, is also expressed in the adult vertebrate nervous system and up-regulated in injured peripheral nervous system cells. KIF4A is detected both in the cell bodies and regrowing axons of injured neurons, consistent with its function as an axonal transporter of cargoes such as β1-integrin and L1CAM. Our study further demonstrates that KIF4A levels are greatly increased in Schwann cells from injured distal nerve stumps, particularly at a time when they are reprogrammed into an essential proliferative repair phenotype. Moreover, Kif4a mRNA levels were approximately ~6-fold higher in proliferative cultured Schwann cells compared with non-proliferative ones. A hypothesized function for Kif4a in Schwann cell proliferation was further confirmed by Kif4a knockdown, as this significantly reduced Schwann cell proliferation in vitro. Our findings show that KIF4A is expressed in adult vertebrate nervous systems and is up-regulated following peripheral injury. The timing of KIF4A up-regulation, its location during regeneration, and its proliferative role, all suggest a dual role for this protein in neuroregeneration that is worth exploring in the future.

Key words: axonal regrowth, KIF4 kinesin, nerve tissue regeneration, neural regeneration, peripheral nerve injury, repair, Schwann cells