MicroRNA-26a supports mammalian axon regeneration in vivo by suppressing GSK3β expression

J. J. Jiang, C. M. Liu, B. Y. Zhang, X. W. Wang, M. Zhang, Saijilafu, S. R. Zhang, P. Hall, Y. W. Hu, F. Q. Zhou

Research output: Contribution to journalArticlepeer-review

Abstract

MicroRNAs are emerging to be important epigenetic factors that control axon regeneration. Here, we report that microRNA-26a (miR-26a) is a physiological regulator of mammalian axon regeneration in vivo. We demonstrated that endogenous miR-26a acted to target specifically glycogen synthase kinase 3β (GSK3β) in adult mouse sensory neurons in vitro and in vivo. Inhibition of endogenous miR-26a in sensory neurons impaired axon regeneration in vitro and in vivo. Moreover, the regulatory effect of miR-26a was mediated by increased expression of GSK3β because downregulation or pharmacological inhibition of GSK3β fully rescued axon regeneration. Our results also suggested that the miR-26a-GSK3β pathway regulated axon regeneration at the neuronal soma by controlling gene expression. We provided biochemical and functional evidences that the regenerationassociated transcription factor Smad1 acted downstream of miR-26a and GSK3β to control sensory axon regeneration. Our study reveals a novel miR-26a-GSK3β-Smad1 signaling pathway in the regulation of mammalian axon regeneration. Moreover, we provide the first evidence that, in addition to inhibition of GSK3β kinase activity, maintaining a lower protein level of GSK3β in neurons by the microRNA is necessary for efficient axon regeneration.

Original languageEnglish (US)
Article numbere1865
JournalCell Death and Disease
Volume6
Issue number8
DOIs
StatePublished - Aug 27 2015

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Fingerprint Dive into the research topics of 'MicroRNA-26a supports mammalian axon regeneration in vivo by suppressing GSK3β expression'. Together they form a unique fingerprint.

Cite this