title: MicroRNA-26a supports mammalian axon regeneration in vivo by suppressing GSK3β 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 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.
authors: Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People's Republic of China.|Department of Orthopaedic Surgery and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors: J-J
authors: JJ
authors: Jiang
authors: Department of Orthopaedic Surgery and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.|State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100190, People's Repubic of China.
authors: C-M
authors: CM
authors: Liu
authors: Department of Orthopaedic Surgery and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors: B-Y
authors: BY
authors: Zhang
authors: Department of Orthopaedic Surgery and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors: X-W
authors: XW
authors: Wang
authors: Department of Orthopaedic Surgery and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors: M
authors: M
authors: Zhang
authors: Department of Orthopaedic Surgery and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.|Department of Orthopaedics, the First Affiliated Hospital, Orthopaedic Institute, Soochow University, Suzhou 215123, Jiangsu, People's Republic of China.
authors: Saijilafu
authors: Department of Orthopaedic Surgery and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors: S-R
authors: SR
authors: Zhang
authors: Department of Orthopaedic Surgery and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors: P
authors: P
authors: Hall
authors: Department of Orthopaedic Surgery and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors: Y-W
authors: YW
authors: Hu
authors: Department of Orthopaedic Surgery and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.|The Solomon H Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore 21287, MD, USA.
authors: F-Q
authors: FQ
authors: Zhou
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000235:genetics*; D011984:Sensory Receptor Cells / Q000378:metabolism* / Q000648:ultrastructure; D015398:Signal Transduction; D051898:Smad1 Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D035683:MicroRNAs; C543693:Mirn26 microRNA, mouse; D016376:Oligonucleotides, Antisense; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3