title: Axotomy-induced miR-21 promotes axon growth in adult dorsal root ganglion neurons.
abstract: Following injury, dorsal root ganglion (DRG) neurons undergo transcriptional changes so as to adopt phenotypic changes that promote cell survival and axonal regeneration. Here we used a microarray approach to profile changes in a population of small noncoding RNAs known as microRNAs (miRNAs) in the L4 and L5 DRG following sciatic nerve transection. Results showed that 20 miRNA transcripts displayed a significant change in expression levels, with 8 miRNAs transcripts being altered by more than 1.5-fold. Using quantitative reverse transcription PCR, we demonstrated that one of these miRNAs, miR-21, was upregulated by 7-fold in the DRG at 7 days post-axotomy. In dissociated adult rat DRG neurons lentiviral vector-mediated overexpression of miR-21 promoted neurite outgrowth on a reduced laminin substrate. miR-21 directly downregulated expression of Sprouty2 protein, as confirmed by Western blot analysis and 3' untranslated region (UTR) luciferase assays. Our data show that miR-21 is an axotomy-induced miRNA that enhances axon growth, and suggest that miRNAs are important players in regulating growth pathways following peripheral nerve injury.
authors.affiliation: School of Clinical Sciences, University of Bristol, Bristol, United Kingdom.
authors.forename: Iain T
authors.initials: IT
authors.lastname: Strickland
authors.forename: Louise
authors.initials: L
authors.lastname: Richards
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Holmes
authors.forename: David
authors.initials: D
authors.lastname: Wynick
authors.forename: James B
authors.initials: JB
authors.lastname: Uney
authors.forename: Liang-Fong
authors.initials: LF
authors.lastname: Wong
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism*; D019771:Axotomy; D005727:Ganglia, Spinal / Q000378:metabolism*; D020869:Gene Expression Profiling; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D016501:Neurites / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; C531950:MIRN21 microRNA, mouse; D008565:Membrane Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; C404992:Spry2 protein, rat; C546082:mirn21 microRNA, rat; D017346:Protein Serine-Threonine Kinases; C118389:Spry2 protein, mouse