| First Author | Jia L | Year | 2018 |
| Journal | Mol Neurobiol | Volume | 55 |
| Issue | 12 | Pages | 9089-9099 |
| PubMed ID | 29637443 | Mgi Jnum | J:345261 |
| Mgi Id | MGI:6835533 | Doi | 10.1007/s12035-018-1047-3 |
| Citation | Jia L, et al. (2018) MiR-34a Regulates Axonal Growth of Dorsal Root Ganglia Neurons by Targeting FOXP2 and VAT1 in Postnatal and Adult Mouse. Mol Neurobiol 55(12):9089-9099 |
| abstractText | Hyperglycemia impairs nerve fibers of dorsal root ganglia (DRG) neurons, leading to diabetic peripheral neuropathy (DPN). However, the molecular mechanisms underlying DPN are not fully understood. Using a mouse model of type II diabetes (db/db mouse), we found that microRNA-34a (miR-34a) was over-expressed in DRG, sciatic nerve, and foot pad tissues of db/db mice. In vitro, high glucose significantly upregulated miR-34a in postnatal and adult DRG neurons, which was associated with inhibition of axonal growth. Overexpression and attenuation of miR-34a in postnatal and adult DRG neurons suppressed and promoted, respectively, axonal growth. Bioinformatic analysis suggested that miR-34a putatively targets forkhead box protein P2 (FOXP2) and vesicle amine transport 1 (VAT1), which were decreased in diabetic tissues and in cultured DRG neurons under high glucose conditions. Dual-luciferase assay showed that miR-34a downregulated FOXP2 and VAT1 expression by targeting their 3' UTR. Gain-of- and loss-of-function analysis showed an inverse relation between augmentation of miR-34a and reduction of FOXP2 and VAT1 proteins in postnatal and adult DRG neurons. Knockdown of FOXP2 and VAT1 reduced axonal growth. Together, these findings suggest that miR-34a and its target genes of FOXP2 and VAT1 are involved in DRG neuron damage under hyperglycemia. |
