| Author |
Jiang, J-J Liu, C-M Zhang, B-Y Wang, X-W Zhang, M. Zhang, S-R Hall, P. Hu, Y-W Zhou, F-Q |
| Description |
Author Affiliation: Jiang JJ ( Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People's Republic of China.); Liu CM ( Department of Orthopaedic Surgery and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.); Zhang BY ( Department of Orthopaedic Surgery and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.); Wang XW ( State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100190, People's Repubic of China.); Zhang M ( Department of Orthopaedic Surgery and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.); Saijilafu ( Department of Orthopaedic Surgery and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.); Zhang SR ( Department of Orthopaedic Surgery and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.); Hall P ( Department of Orthopaedic Surgery and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.); Hu YW ( Department of Orthopaedics, the First Affiliated Hospital, Orthopaedic Institute, Soochow University, Suzhou 215123, Jiangsu, People's Republic of China.); Zhou FQ ( Department of Orthopaedic Surgery and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.) |
| 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 3ß (GSK3ß) 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 GSK3ß because downregulation or pharmacological inhibition of GSK3ß fully rescued axon regeneration. Our results also suggested that the miR-26a-GSK3ß 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 GSK3ß to control sensory axon regeneration. Our study reveals a novel miR-26a-GSK3ß-Smad1 signaling pathway in the regulation of mammalian axon regeneration. Moreover, we provide the first evidence that, in addition to inhibition of GSK3ß kinase activity, maintaining a lower protein level of GSK3ß in neurons by the microRNA is necessary for efficient axon regeneration. |
| Subject Keyword |
Research Support, N.i.h., Extramural Micrornas Green Fluorescent Proteins Research Support, Non-u.s. Gov't Enzyme Inhibitors Oligonucleotides, Antisense Signal Transduction Gene Expression Regulation Glycogen Synthase Kinase 3 Pharmacology Metabolism Antagonists & Inhibitors Sensory Receptor Cells Discipline Cell Biology Axons Regeneration Animals Smad1 Protein Ultrastructure Genetics Mice Genes, Reporter |
