Journal
NEUROCHEMICAL RESEARCH
Volume 43, Issue 11, Pages 2038-2046Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11064-018-2625-5
Keywords
MicroRNA; Spinal cord injury; Lentivirus; MiR-29a; PTEN; Axonal regeneration
Categories
Funding
- National Science Foundation of China [81471263]
- Natural Science Foundation of Jiangsu Province [BK20151177]
- Changzhou High-Level Medical Talents Training Project [2016ZCLJ005]
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MicroRNAs as a novel class of endogenous small non-coding RNAs, modulate negative gene expression at the post-transcriptional level. Our previous work has demonstrated that miR-29a reduces PTEN expression by directly targeting the 3-UTRs (untranslated regions) of its mRNA, thus promoting neurite outgrowth. To further confirm the role of miR-29a in the recovery of SCI and its potential mechanisms, a recombinant lentiviral vector was used to promote miR-29a expression in the injured spinal cord. As compared with the LV-eGFP group and normal saline group, a significantly increased level of miR-29a expression and a markedly decreased level of PTEN expression were observed in the LV-miR-29a group. Overexpression of miR-29a increased the phosphorylation of two proteins (Akt and S6) of PI3K-AKT-mTOR signaling pathway and the expression of axonal regeneration associated key marker protein (neurofiament-200). Moreover, quantitative imaging analysis was performed to confirm that LV-miR-29a group expressed axonal regeneration at 4.0 +/- 0.2-fold as much as the other two groups. Besides, miR-29a overexpression promoted hindlimb motor functional recovery. Collectively, these results suggested that miR-29a may be an important regulator for axon regeneration, and a potential therapeutic target for SCI recovery.
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