Temporal changes in the spinal cord transcriptome after peripheral nerve injury
Temporal changes in the spinal cord transcriptome after peripheral nerve injury
复制标题
周围神经损伤后脊髓转录组的时间变化
DOI：
10.4103/1673-5374.272618
复制
发表时间：
2020-07-01
影响因子：
6.1
通讯作者：
Yin, Xiao-Feng
中科院分区：
文献类型：
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作者：
Weng, Jian;Li, Dong-Dong;Yin, Xiao-Feng
周围神经损伤可能引发脊髓中mRNA水平的变化。寻找关键的mRNA对于改善神经损伤后的修复非常重要。本研究旨在通过转录组学分析研究坐骨神经损伤后脊髓中mRNA的变化。建立C57 BL/6小鼠左侧坐骨神经失神经支配模型。分别于术后0、1、2、4、8周取左侧L4-6脊髓节段。通过RNA测序生成mRNA表达谱。采用生物信息学方法比较坐骨神经切断后1、2、4、8周与0周脊髓mRNA的测序结果。我们鉴定了1915个在脊髓中差异表达的mRNA，其中4个、1909个和2个分别在坐骨神经损伤后1周、4周和8周差异表达。测序结果显示，坐骨神经损伤后4周，脊髓中差异表达的mRNA数量最多。这些mRNA与细胞对脂质的反应、ATP代谢、能量偶联质子跨膜转运、核转录因子复合物、液泡质子转运V型ATP酶复合物、线粒体内膜蛋白复合物、tau蛋白结合、NADH脱氢酶活性和氢离子跨膜转运蛋白活性有关。其中，Sgk 1、Neurturin和Gpnmb参与了细胞的生长发育。通路分析表明，这些mRNA主要参与醛固酮调节的钠重吸收、氧化磷酸化和集合管酸分泌。功能评估表明这些mRNA与炎症和细胞形态发育相关。我们的研究结果表明，周围神经损伤后不同时间点参与变化的脊髓mRNA的数量和类型是不同的。坐骨神经损伤后4周，脊髓中差异表达的mRNA数量最高。这些结果为寻找治疗周围神经损伤的新靶点，以及进一步开展周围神经损伤与修复的基因治疗研究提供了参考数据。本研究程序于2017年3月5日获得北京大学人民医院伦理委员会批准（批件号：2017 PHC 004）。
Peripheral nerve injury may trigger changes in mRNA levels in the spinal cord. Finding key mRNAs is important for improving repair after nerve injury. This study aimed to investigate changes in mRNAs in the spinal cord following sciatic nerve injury by transcriptomic analysis. The left sciatic nerve denervation model was established in C57BL/6 mice. The left L4–6 spinal cord segment was obtained at 0, 1, 2, 4 and 8 weeks after severing the sciatic nerve. mRNA expression profiles were generated by RNA sequencing. The sequencing results of spinal cord mRNA at 1, 2, 4, and 8 weeks after severing the sciatic nerve were compared with those at 0 weeks by bioinformatic analysis. We identified 1915 differentially expressed mRNAs in the spinal cord, of which 4, 1909, and 2 were differentially expressed at 1, 4, and 8 weeks after sciatic nerve injury, respectively. Sequencing results indicated that the number of differentially expressed mRNAs in the spinal cord was highest at 4 weeks after sciatic nerve injury. These mRNAs were associated with the cellular response to lipid, ATP metabolism, energy coupled proton transmembrane transport, nuclear transcription factor complex, vacuolar proton-transporting V-type ATPase complex, inner mitochondrial membrane protein complex, tau protein binding, NADH dehydrogenase activity and hydrogen ion transmembrane transporter activity. Of these mRNAs, Sgk1, Neurturin and Gpnmb took part in cell growth and development. Pathway analysis showed that these mRNAs were mainly involved in aldosterone-regulated sodium reabsorption, oxidative phosphorylation and collecting duct acid secretion. Functional assessment indicated that these mRNAs were associated with inflammation and cell morphology development. Our findings show that the number and type of spinal cord mRNAs involved in changes at different time points after peripheral nerve injury were different. The number of differentially expressed mRNAs in the spinal cord was highest at 4 weeks after sciatic nerve injury. These results provide reference data for finding new targets for the treatment of peripheral nerve injury, and for further gene therapy studies of peripheral nerve injury and repair. The study procedures were approved by the Ethics Committee of the Peking University People’s Hospital (approval No. 2017PHC004) on March 5, 2017.