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 regeneration-associated 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.

Based on the different nucleation ability, different contents and proportions of the mixed nucleating agents were melt compounded with pure isotactic polypropylene resins employed in this work, selective b nucleating agent was ac ompound of pimelic acid and calcium stearate, the a nucleating agent was a type of dibenzylidene sorbitol derivative. The competition attributed to the different type of interactions between an ucleating agent and isotactic polypropylene molecular chains during crystallization was investigated in this research. For alow content of the mixed nucleating agents used, a nucleation dominated the crystallization behavior of isotactic polypropylene, while with an increase of the content of the mixed nucleating agents, the situation was reversed and b nucleation became dominant. In the b dominated region, both of the molecular chain and segmental motions were various with different nucleating agent proportion. Thus, the content and proportion of the components of the nucleating agents were the critical factors in the competition during crystallization.