Sensory dysfunction post spinal cord injury causes patients great distress. Sciatic nerve conditioning injury (SNCI) has been shown to restore sensory function after spinal cord dorsal column injury (SDCL); however, the underlying mechanism of this recovery remains unclear. We performed a microarray assay to determine the associated miRNAs that might regulate the process of SNCI promoting SDCL repair. In total, 13 miRNAs were identified according to our inclusion criteria, and RT-qPCR was used to verify the microarray results. Among the 13 miRNAs, the miR-155-5p levels were decreased at 9 h, 3 d, 7 d, 14 d, 28 d, 2 m and 3 m timepoints in the SDCL group, while the SNCI group had a smaller decrease. Thus, miR-155-5p was chosen for further study after a literature review and an analysis with the TargetScan online tool. Specifically, miR-155-5p targets PKI-α, and the expression pattern of PKI-α was opposite that of miR-155-5p in both the SDCL and SNCI groups. Interestingly, miR-155-5p could promote dorsal root ganglion (DRG) neuron axon growth via the cAMP/PKA pathway and in a TNF-α, IL-1β or MAG inhibitory microenvironment in vitro. Furthermore, miR-155-5p could regulate the cAMP/PKA pathway and promote sensory conduction function recovery post dorsal column injury as detected by NF-200 immunohistochemistry, somatosensory-evoked potentials, BBB scale and tape removal test. Collectively, our results demonstrated that miR-155-5p participates in the molecular mechanism by which SNCI promotes the repair of SDCL and that upregulated miR-155-5p can repair SDCL by enhancing DRG neuron axon growth via the cAMP/PKA pathway. These findings suggest a novel treatment target for spinal cord injury.

Spinal cord injury (SCI) induces both motor and sensory dysfunctions. We wondered whether miR‐30b could promote primary sensory neuron (PSN) axon growth in inhibitory microenvironment. The neurite growth was promoted by miR‐30b agomir and inhibited by antagomir. MiR‐30b targeted and degraded sema3A mRNA. MiR‐30b regulated the formation of sema3A‐NRP‐1‐PlexinA1 complex via targeting sema3A. The neurite length was induced by the miR‐30b agomir, and the application of sema3A protein could reverse the effect of agomir. GTP‐RhoA and ROCK expression were down‐regulated by miR‐30b. Neurite outgrowth that inhibited by sema3A and the miR‐30b antagomir was increased by Y‐27632. Agomir promoted neurite growth in NogoA inhibitory conditions, which indicated miR‐30b could both enhance neuronal intrinsic regenerative ability and promote neurite growth against inhibitory microenvironment via Sema3A/NRP‐1/PlexinA1/RhoA/ROCK axis. The agomir could also regulate Sema3A/NRP‐1/PlexinA1/RhoA/ROCK axis in vivo and restore spinal cord sensory conductive function. In conclusion, miR‐30b could be a novel target for sensation recovery after SCI.

The present study explored a key miRNA that plays a vital role in sciatic nerve conditioning injury promoting repair of injured dorsal column, and validated its function. Microarray analysis revealed miR-17-5p expression decreased sharply at 3, 7 and 14 days in the sciatic nerve conditioning injury group compared with the simple dorsal column lesion group. After miR-17-5p inhibition in DRG neurons, GAP-43 expression was upregulated and neurite growth was increased. STAT3 together with p-STAT3 showed opposite trends with miR-17-5p. MiR-17-5p inhibition extended neurite and upregulated STAT3, p-STAT3 and GAP-43. To further determine a substitution therapy for sciatic nerve conditioning injury, beta-phenethyl isothiocyanate (PEITC), which downregulates miR-17-5p, was assessed. The results showed that treatment with 10 µM PEITC resulted in longest neurite length. Further experiments demonstrated PEITC induced neurite growth by inhibiting miR-17-5p and further upregulating STAT3, p-STAT3 and GAP-43. The somatosensory evoked potential test confirmed similar treatment effects for PEITC, Ad-miRNA-17-5p inhibitor, and sciatic nerve conditioning injury on the dorsal column lesion. In conclusion, the miR-17-5p/STAT3/GAP-43 axis is an indispensable component of sciatic nerve conditioning injury promoting repair of injured dorsal column. PEITC could promote repair of injured dorsal column via the miR-17-5p/STAT3/GAP-43 axis, and could mimic the treatment effect of sciatic nerve conditioning injury.