中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (10): 2267-2271.doi: 10.4103/1673-5374.336874

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

大鼠损伤脊髓远端和近端差异表达基因

  

  • 出版日期:2022-10-15 发布日期:2022-03-16
  • 基金资助:
    江苏省研究生科研与实践创新计划(KYCX-2065)

A comparative analysis of differentially expressed genes in rostral and caudal regions after spinal cord injury in rats

Xue-Min Cao, Sheng-Long Li, Yu-Qi Cao, Ye-Hua Lv, Ya-Xian Wang, Bin Yu, Chun Yao   

  1. Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China
  • Online:2022-10-15 Published:2022-03-16
  • Contact: Chun Yao, PhD, yaochun@ntu.edu.cn; Bin Yu, PhD, yubin@ntu.edu.cn.
  • Supported by:
    This work was supported by Postgraduate Research & Practice Innovation Program of Jiangsu Province, No. KYCX-2065 (to XMC).

摘要:

继发性脊髓损伤是一个由多个系统和细胞参与的复杂过程,探索伤后的分子和生物过程的改变对治疗的发展至关重要;然而,SCI病变周围的远端和近端差异表达基因的研究却较少见。在此,实验分析了损伤脊髓远端和近端差异表达基因(DEGs),以获得SCI后这两个区段的不同生物过程。发现脊髓损伤后近端和远端有11组差异基因,包括Col3a1, Col1a1,Dcn,Fn1,Lox,Postn,Tnc,Isl2,Isl1,Kcnk3 和 Nrg1。功能富集分析表明,在脊髓损伤后0.5 小时,近端首先发生免疫反应, 随后发生机械应激反应,血管发育和伤口愈合等生物过程。同时,在远端上调的差异表达基因中,涉及的生物过程包括钾离子的跨膜转运和脑发育。在第14天,细胞对TGFβ刺激的反应发生在近端,远端涉及神经元细胞命运决定。脊髓损伤后3天到14天,血管发育发生在近端,这说明血管发生首先在近端中出现。另外,与后期的近端相比,参与神经元命运和突触传递的基因在远端占更多的主导作用。然后选择这些生物学过程中的关键基因Col1a1, Col3a1,Dcn,Fn1,Kcnk3 和 Nrg1进行qRT-PCR和Fn1免疫荧光染色验证。结果揭示了在脊髓损伤后的近端和远端富集的不同的生物学事件,为SCI的病理学研究提供了新的治疗靶点和切入点。

https://orcid.org/0000-0002-8927-3333 (Bin Yu); https://orcid.org/0000-0002-3706-955X (Chun Yao)

Abstract: The initial mechanical damage of a spinal cord injury (SCI) triggers a progressive secondary injury cascade, which is a complicated process integrating multiple systems and cells. It is crucial to explore the molecular and biological process alterations that occur after SCI for therapy development. The differences between the rostral and caudal regions around an SCI lesion have received little attention. Here, we analyzed the differentially expressed genes between rostral and caudal sites after injury to determine the biological processes in these two segments after SCI. We identified a set of differentially expressed genes, including Col3a1, Col1a1, Dcn, Fn1, Kcnk3, and Nrg1, between rostral and caudal regions at different time points following SCI. Functional enrichment analysis indicated that these genes were involved in response to mechanical stimulus, blood vessel development, and brain development. We then chose Col3a1, Col1a1, Dcn, Fn1, Kcnk3, and Nrg1 for quantitative real-time PCR and Fn1 for immunostaining validation. Our results indicate alterations in different biological events enriched in the rostral and caudal lesion areas, providing new insights into the pathology of SCI.

Key words: biological process, caudal, differentially expressed genes, Gene Ontology, hemisection, immunostaining, Rattus norvegicus, RNA-sequencing, rostral, spinal cord injury