Abstract
Spinal cord injury (SCI) causes sensory dysfunctions such as paresthesia, dysesthesia, and chronic neuropathic pain. MiR-20a facilitates the axonal outgrowth of the cortical neurons. However, the role of miR-20a in the axonal outgrowth of primary sensory neurons and spinal cord dorsal column lesion (SDCL) is yet unknown. Therefore, the role of miR-20a post-SDCL was investigated in rat. The NF-200 immunofluorescence staining was applied to observe whether axonal outgrowth of dorsal root ganglion (DRG) neurons could be altered by miR-20a or PDZ-RhoGEF modulation in vitro. The expression of miR-20a was quantized with RT-PCR. Western blotting analyzed the expression of PDZ-RhoGEF/RhoA/GAP43 axis after miR-20a or PDZ-RhoGEF was modulated. The spinal cord sensory conduction function was assessed by somatosensory-evoked potentials and tape removal test. The results demonstrated that the expression of miR-20a decreased in a time-dependent manner post-SDCL. The regulation of miR-20a modulated the axonal growth and the expression of PDZ-RhoGEF/RhoA/GAP43 axis in vitro. The in vivo regulation of miR-20a altered the expression of miR-20a-PDZ-RhoGEF/RhoA/GAP43 axis and promoted the recovery of ascending sensory function post-SDCL. The results indicated that miR-20a/PDZ-RhoGEF/RhoA/GAP43 axis is associated with the pathophysiological process of SDCL. Thus, targeting the miR-20a/PDZ-RhoGEF /RhoA/GAP43 axis served as a novel strategy in promoting the sensory function recovery post-SCI.
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Acknowledgements
This work was supported by the General Program of Natural Science Foundation of Hebei Province of China (Grant Number H2017101030), the Medical Science and Technology Youth Cultivation Project of the Chinese People’s Liberation Army (Grant Numbers 16QNP074 and 13QNP017), the Research and Development of Science and Technology Program Supported by Chengde Government (Grant Number 201606A062), the Beijing Municipal Education Commission General Project (KM201710025028), the Capital characteristic project (Z161100000116064), and the Public Experiment Training Foundation of Beijing Luhe Hospital, Capital Medical University, China (Grant Number lh201425Shi).
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XG, XZ and XC designed this study; ZW was in charge of the methodology; LC and MY were in charge of the software and validation; Formal analysis was done by YX; ZZ and WL were in charge of the investigation; FW was in charge of data curation; BL wrote the original draft; TW reviewed and edited the draft; XY was in charge of the visualization; YZ and XY supervised the study; TW administrated this study; Funding was acquired from TW; ZW, YZ and XC.
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ARRIVE guidelines and National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publications no. 85-23, revised 1996) for the care and use of animals were followed. All protocols performed in this study were approved by the Ethics Committee of the 266th Hospital of the Chinese People’s Liberation Army (Approval No. 20170038).
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Wang, T., Li, B., Yuan, X. et al. MiR-20a Plays a Key Regulatory Role in the Repair of Spinal Cord Dorsal Column Lesion via PDZ-RhoGEF/RhoA/GAP43 Axis in Rat. Cell Mol Neurobiol 39, 87–98 (2019). https://doi.org/10.1007/s10571-018-0635-0
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DOI: https://doi.org/10.1007/s10571-018-0635-0