Zhu Zhuangchen, Wang Defeng, Jiao Wei, Chen Guang, Cao Yan, Zhang Qingfu, Wang Junqin
Department of Orthopedics, Affiliated Hospital of Taishan Medical University, 271000, China.
Department of Orthopedics, Affiliated Hospital of Taishan Medical University, 271000, China.
Acta Histochem. 2017 Sep;119(7):663-670. doi: 10.1016/j.acthis.2017.07.007. Epub 2017 Aug 26.
This study aimed to explore the potential genes and pathways regulated in spinal cord injury (SCI) model mice with IL-1α and IL-1β knockout (KO).
Gene expression profile GSE70302, which includes data from injured spinal cord of 4 IL-1α-KO mice, 4 IL-1β-KO mice and 4 C57BL with 6 mice as controls was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) of the IL-1α-KO or IL-1β-KO vs. control, and IL-1α-KO vs. IL-1β-KO groups were screened, followed by function enrichment and protein-protein interaction (PPI) analyses. Finally, miRNAs associated with SCI that may target the DEGs were predicted.
A total of 579 and 992 DEGs were selected from the IL-1α-KO vs. control group and the IL-1β-KO vs. control group, respectively, and 208 genes common between the 2 comparison groups were identified. Additionally, 526 DEGs were identified from the IL-1α-KO vs. IL-1β-KO groups. These DEGs were significantly enriched in functions and pathways associated with ion transport, neuron apoptotic processes and inflammatory responses. The common genes were enriched in the pathways for cytokine-cytokine receptor interaction. DEGs of IL-1α-KO vs. IL-1β-KO were significantly enriched in the immune system, hematopoietic cell lineage and PI3K-Akt signalling pathway-associated biological processes and pathways. The PPI network consisted of 76 nodes, such as Saa2, Kcna1, Scn8a, Ccl5, Ccl28 and Pink1. A total of 94 miRNAs, including mir-17-5P and mir-30a-5p were predicted that could target the DEGs.
IL-1α and IL-1β may play important roles in SCI by regulating ion transport, inflammation and neuron apoptotic processes and their associated genes or miRNAs. Compared with IL-1β-KO, IL-1α-KO may improve the outcome of SCI via the alteration of hematopoietic cell lineage and PI3K-Akt signalling pathways.
本研究旨在探索白细胞介素-1α(IL-1α)和白细胞介素-1β(IL-1β)基因敲除(KO)的脊髓损伤(SCI)模型小鼠中调控的潜在基因和信号通路。
从基因表达综合数据库下载基因表达谱GSE70302,其中包括4只IL-1α基因敲除小鼠、4只IL-1β基因敲除小鼠和4只C57BL对照小鼠脊髓损伤的数据。筛选IL-1α基因敲除组或IL-1β基因敲除组与对照组以及IL-1α基因敲除组与IL-1β基因敲除组之间的差异表达基因(DEGs),随后进行功能富集和蛋白质-蛋白质相互作用(PPI)分析。最后,预测可能靶向DEGs的与SCI相关的微小RNA(miRNAs)。
分别从IL-1α基因敲除组与对照组以及IL-1β基因敲除组与对照组中筛选出579个和992个DEGs,并鉴定出两个比较组之间共有的208个基因。此外,从IL-1α基因敲除组与IL-1β基因敲除组中鉴定出526个DEGs。这些DEGs在与离子转运、神经元凋亡过程和炎症反应相关的功能和信号通路中显著富集。共有基因在细胞因子-细胞因子受体相互作用通路中富集。IL-1α基因敲除组与IL-1β基因敲除组的DEGs在免疫系统、造血细胞谱系以及PI3K-Akt信号通路相关的生物学过程和信号通路中显著富集。PPI网络由76个节点组成,如血清淀粉样蛋白A2(Saa2)、钾通道亚家族A成员1(Kcna1)、电压门控钠通道8型(Scn8a)、趋化因子C-C基序配体5(Ccl5)、趋化因子C-C基序配体28(Ccl28)和PTEN诱导激酶1(Pink1)。共预测出94个可靶向DEGs的miRNAs,包括mir-17-5P和mir-30a-5p。
IL-1α和IL-1β可能通过调控离子转运、炎症和神经元凋亡过程及其相关基因或miRNAs在SCI中发挥重要作用。与IL-1β基因敲除相比,IL-1α基因敲除可能通过改变造血细胞谱系和PI3K-Akt信号通路改善SCI的预后。