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Circular RNAs expression profiles and potential key molecules incompletely transected spinal cord injury.

ABSTRACT: Circular RNA is implicated in numerous diseases and conditions, including traumatic injury to the central nervoussystem. However, we know little regarding their role in completely transected spinal cord injury (SCI). Our studyused high-throughput sequencing to analyze circular RNA expression in rats after experimental completetransection of spinal cord. We found differential expression in 400 circular RNAs after SCI, with 249 significantlyup-regulated and 151 significantly down-regulated. We then selected five circular RNAs for qRT-PCR validation,and the results were in agreement with RNA sequencing. Additionally, we predicted the function of circular RNAin SCI through GO and KEGG analyses, as well as the construction of circRNA/microRNA interaction networks.Furthermore, we identified circular RNA chr9:1829226-1834212 and mRNA Hdac11 as key molecules after SCI.In conclusion, this study is the first to characterize circular RNA function in rats after completely transected SCI,through identifying their differential expression. Our results provide insight into the mechanism and therapeutictargets of SCI.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE156999 | GEO | 2020/08/28

REPOSITORIES: GEO

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Project description:Spinal cord injury (SCI) often leads to persistent functional deficits due to severe neuron and glial loss, and to limited axonal regeneration after injury. Here we show that the transplantation of human dental stem cells into the completely transected adult rat spinal cord resulted in a significant recovery of hindlimb locomotor functions. These stem cells exhibited three major neuro-regenerative activities. First, they inhibited the SCI-induced apoptosis of neurons, astrocytes, and oligodendrocytes, improving the preservation of neuronal filaments and myelin sheaths. Second, they promoted the regeneration of transected axons by directly inhibiting multiple axon growth inhibitors, including chondroitin sulfate proteoglycan and myelin-associated glycoprotein, by paracrine mechanisms. Third, they replaced lost cells by differentiating into mature oligodendrocytes under the extreme conditions of SCI. Our data demonstrate that tooth-derived stem cells may provide novel therapeutic benefits for treating SCI through both cell-autonomous and paracrine neuro-regenerative activities. Human dental stem cells were isolated from exfoliated deciduous teeth extracted for clinical purposes were collected at Nagoya University School of Medicine, under approved guidelines set by Nagoya University (H-73, 2003). The ethics committee of Nagoya University approved the experimental protocols (permission number 8-2). Mesenchymal stem cells of human Bone marrow line were obtained from Lonza. Total RNAs were isolated and quantified by spectrophotometer. RNA integrity was checked on 1% agarose gels. RT reactions were carried out with Superscript III reverse transcriptase (Invitrogen) using 1 μg of total RNA in a 50 μl total reaction volume. Microarray experiments were carried out using a CodeLink™ Human Whole Genome Bioarray (Applied Microarrays, Inc. Tempe, AZ) at Filgen, Inc. (Nagoya, Japan). The arrays were scanned using a GenePix4000B Array Scanner (Molecular Devices, Sunnyvale, CA), and the data was analyzed by using MicroArray Data Analysis Tool Ver3.2 (Filgen, Inc.).

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Circular RNAs expression profiles and potential key molecules incompletely transected spinal cord injury.

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