期刊
CELL DEATH & DISEASE
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cddis.2015.239
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资金
- NIH [R01NS064288, R01NS085176, R01GM111514]
- Craig H Neilsen Foundation
- Maryland Stem Cell Research Fund
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM111514] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS064288, R01NS085176] Funding Source: NIH RePORTER
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 3 beta (GSK3 beta) 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 GSK3 beta because downregulation or pharmacological inhibition of GSK3 beta fully rescued axon regeneration. Our results also suggested that the miR-26a-GSK3 beta pathway regulated axon regeneration at the neuronal soma by controlling gene expression. We provided biochemical and functional evidences that the regeneration-associated transcription factor Smad1 acted downstream of miR-26a and GSK3 beta to control sensory axon regeneration. Our study reveals a novel miR-26a-GSK3 beta-Smad1 signaling pathway in the regulation of mammalian axon regeneration. Moreover, we provide the first evidence that, in addition to inhibition of GSK3 beta kinase activity, maintaining a lower protein level of GSK3 beta in neurons by the microRNA is necessary for efficient axon regeneration.
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