Shi Ling-Ling, Zhang Nan, Xie Xiu-Mei, Chen Yue-Juan, Wang Rui, Shen Lin, Zhou Jian-Sheng, Hu Jian-Guo, Lü He-Zuo
Clinical Laboratory, the First Affiliated Hospital of Bengbu Medical College, Anhui, 233004, People's Republic of China.
Department of Immunology, Bengbu Medical College, Anhui, 233030, People's Republic of China.
BMC Genomics. 2017 Feb 15;18(1):173. doi: 10.1186/s12864-017-3532-x.
Spinal cord injury (SCI) results in fatal damage and currently has no effective treatment. The pathological mechanisms of SCI remain unclear. In this study, genome-wide transcriptional profiling of spinal cord samples from injured rats at different time points after SCI was performed by RNA-Sequencing (RNA-Seq). The transcriptomes were systematically characterized to identify the critical genes and pathways that are involved in SCI pathology.
RNA-Seq results were obtained from total RNA harvested from the spinal cords of sham control rats and rats in the acute, subacute, and chronic phases of SCI (1 day, 6 days and 28 days after injury, respectively; n = 3 in every group). Compared with the sham-control group, the number of differentially expressed genes was 1797 in the acute phase (1223 upregulated and 574 downregulated), 6590 in the subacute phase (3460 upregulated and 3130 downregulated), and 3499 in the chronic phase (1866 upregulated and 1633 downregulated), with an adjusted P-value <0.05 by DESeq. Gene ontology (GO) enrichment analysis showed that differentially expressed genes were most enriched in immune response, MHC protein complex, antigen processing and presentation, translation-related genes, structural constituent of ribosome, ion gated channel activity, small GTPase mediated signal transduction and cytokine and/or chemokine activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the most enriched pathways included ribosome, antigen processing and presentation, retrograde endocannabinoid signaling, axon guidance, dopaminergic synapses, glutamatergic synapses, GABAergic synapses, TNF, HIF-1, Toll-like receptor, NF-kappa B, NOD-like receptor, cAMP, calcium, oxytocin, Rap1, B cell receptor and chemokine signaling pathway.
This study has not only characterized changes in global gene expression through various stages of SCI progression in rats, but has also systematically identified the critical genes and signaling pathways in SCI pathology. These results will expand our understanding of the complex molecular mechanisms involved in SCI and provide a foundation for future studies of spinal cord tissue damage and repair. The sequence data from this study have been deposited into Sequence Read Archive ( http://www.ncbi.nlm.nih.gov/sra ; accession number PRJNA318311).
脊髓损伤（SCI）会导致致命损害，目前尚无有效治疗方法。SCI的病理机制仍不清楚。在本研究中，通过RNA测序（RNA-Seq）对SCI后不同时间点的损伤大鼠脊髓样本进行了全基因组转录谱分析。对转录组进行系统表征以鉴定参与SCI病理过程的关键基因和途径。
从假手术对照组大鼠以及SCI急性期、亚急性期和慢性期大鼠（分别为损伤后1天、6天和28天；每组n = 3）的脊髓中收获的总RNA获得了RNA-Seq结果。与假手术对照组相比，急性期差异表达基因数量为1797个（上调1223个，下调574个），亚急性期为6590个（上调3460个，下调3130个），慢性期为3499个（上调1866个，下调1633个），经DESeq分析调整后的P值<0.05。基因本体（GO）富集分析表明，差异表达基因最富集于免疫应答、MHC蛋白复合体、抗原加工和呈递、翻译相关基因、核糖体结构成分、离子门控通道活性、小GTPase介导的信号转导以及细胞因子和/或趋化因子活性。京都基因与基因组百科全书（KEGG）通路分析表明，最富集的通路包括核糖体、抗原加工和呈递、逆行内源性大麻素信号传导、轴突导向、多巴胺能突触、谷氨酸能突触、GABA能突触、TNF、HIF-1、Toll样受体、NF-κB、NOD样受体、cAMP、钙、催产素、Rap1、B细胞受体和趋化因子信号通路。
本研究不仅表征了大鼠SCI进展各阶段的全局基因表达变化，还系统鉴定了SCI病理过程中的关键基因和信号通路。这些结果将扩展我们对SCI复杂分子机制的理解，并为未来脊髓组织损伤和修复研究提供基础。本研究的序列数据已存入序列读取存档库（http://www.ncbi.nlm.nih.gov/sra；登录号PRJNA318311）。
