Abstract
BackgroundThe prognostic and therapeutic potential of microRNAs (miRNAs) in spinal cord injury (SCI) has aroused increasing concerns. This study aims to research the functions of miR-29a/199B in the neurological function recovery after SCI and the mechanical mechanism.MethodsA rat model with SCI was induced with sham-operated ones as control. The locomotor function and coordination of rat hindlimbs were determined by a Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and a ladder-climbing test, respectively. Expression of a neurofilament protein NF-200 and synaptophysin in gray matter of rats was determined to evaluate neuronal recovery in a cellular perspective. Binding relationships between miR-29a/199B with RGMA were predicted and validated using luciferase assays. Altered expression of miR-29a/199B and RGMA was introduced to explore their functions in rat neurological functions. The protein level and phosphorylation of STAT3 in gray matter were measured by western blot analysis.ResultsmiR-29a and miR-199B were poorly expressed, while RGMA was abundantly expressed in gray matter at injury sites. Either miR-29a or miR-199B could bind to RGMA. Overexpression of miR-29a/199B or silencing of RGMA led to an increase in BBB locomotor scores, hindlimb coordination ability, and the expression of NF-200 and synaptophysin in gray matter. Further inhibition in miR-29a/199B blocked the promoting roles of RGMA silencing in neurological recovery. Upregulation of miR-29a/199B or downregulation of RGMA suppressed the phosphorylation of STAT3.ConclusionThis study evidenced that miR-29a and miR-199B negatively regulated RGMA to suppress STAT3 phosphorylation, therefore promoting the neurological function recovery in rats following SCI.
Highlights
The prognostic and therapeutic potential of microRNAs in spinal cord injury (SCI) has aroused increasing concerns
Results miR-29a and miR-199B were downregulated in rats with SCI As mentioned before, miR-29a and miR-199B were reported to be poorly expressed in rat models with SCI and showed protective roles in neuronal recovery
According to the Reverse transcription-quantitative polymerase chain reaction (RTqPCR) results, miR-29a and miR-199B were poorly expressed in the gray matter in rats with SCI compared to the sham-operated ones (p < 0.05) (Fig. 1)
Summary
The prognostic and therapeutic potential of microRNAs (miRNAs) in spinal cord injury (SCI) has aroused increasing concerns. Even though survive the initial injury, the SCI patients face great risks of medical complications throughout their lives, which is often related to infectious morbidity, leading to significant reductions in life quality and expectancy [2]. MicroRNAs (miRNAs) are reported as one of the important biomarkers associated with the injury severity and prognosis of SCI, which may predict spontaneous neurological recovery over time with high precision, sensitivity, and reproducibility [5]. Thanks to their unique potent function in regulating target gene expression post-transcriptionally, miRNAs are emerging potential tools or targets for SCI treatment with great therapeutic significances [6, 7]. A rat model with SCI was established [16, 17] to validate this hypothesis and to explore whether STAT3 is involved in the events
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