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.

MicroRNA-138 and SIRT1 form a mutual negative feedback loop to regulate mammalian axon regeneration

“…2B). These results are in line with a recent genetic profiling study in which miR-138 was among a group of microRNAs that are down-regulated in DRGs after peripheral nerve injury (Strickland et al 2011). To determine the functional role of miR-138 in axon regeneration, we used a recently developed cellreplating model (Saijilafu and Zhou 2012).…”

“…Several previous studies have shown that miR-34a can target SIRT1 in different tissues (Yamakuchi 2012). However, the expression of miR-34a does not seem to be altered in adult sensory neurons upon peripheral axotomy (Strickland et al 2011;Zhang et al 2011;Zhou et al 2011), suggesting that it is unlikely to target SIRT1, which is up-regulated drastically upon axotomy.…”

“…In mature animals, one study found that sensory axon regeneration in vivo was impaired in animals lacking the Dicer protein, which is crucial for microRNA processing , suggesting that microRNAs are potential novel regulators of axon regeneration. Indeed, several genetic profiling studies (Strickland et al 2011;Zhang et al 2011;Zhou et al 2011) have shown that the expression levels of many microRNAs are changed in adult mouse sensory neurons after the peripheral nerve injury, which leads to enhanced intrinsic axon growth capacity and robust axon regeneration. However, to date, no study has ever reported the roles of microRNAs in the regulation of mammalian axon regeneration in vivo.…”

Role of MicroRNA in Visceral Pain

“…This finding strongly suggests the involvement of miRNAs in long-term cortical plasticity following esophageal acid exposure early in life. Here, we review specific miRNAs that have been identified as the regulators of nociceptive activity and highlight their possible association with pain processing in various pain conditions (Table 87, 99,100,101,103,[105][106][107][108][109][110][111][112][113][114][115][116][117][118][119][120][121][122] ).…”

The brake within: Mechanisms of intrinsic regulation of axon growth featuring the Cdh1-APC pathway

“…Taxol has also proven to stimulate axonal regeneration in models of spinal and optic nerve injury [51,52]. promotes axon growth in adult dorsal root ganglion neurons [63]. Among the microRNAs, that are upregulated in dorsal root ganglia after nerve injury, miR-222 was identified and found to target PTEN [64], suggesting that the injuryresponse disengages inhibitory mechanisms to stimulate regeneration in the PNS, which could be useful in designing therapies for CNS injuries.…”