MicroRNA-26a supports mammalian axon regeneration in vivo by suppressing GSK3? expression.

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 3? (GSK3?) 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? because downregulation or pharmacological inhibition of GSK3? fully rescued axon regeneration. Our results also suggested that the miR-26a-GSK3? 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? to control sensory axon regeneration. Our study reveals a novel miR-26a-GSK3?-Smad1 signaling pathway in the regulation of mammalian axon regeneration. Moreover, we provide the first evidence that, in addition to inhibition of GSK3? kinase activity, maintaining a lower protein level of GSK3? in neurons by the microRNA is necessary for efficient axon regeneration.

SUBMITTER: Jiang JJ 

PROVIDER: S-EPMC4558520 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature