强直性脊柱炎间充质干细胞差异基因的生物信息学分析
Bioinformatics Analysis of Differential Genes in Mesenchymal Stem Cells of Ankylosing Spondylitis
DOI: 10.12677/TCM.2023.1210429, PDF,   
作者: 叶天真：湖北中医药大学第一临床学院，湖北 武汉；李 停*：湖北省中西医结合医院，湖北 武汉
关键词: GEO数据库；强直性脊柱炎；生物信息学；差异基因；间充质干细胞；GEO Database； Ankylosing Spondylitis； Bioinformatics； Differential Gene； Mesenchymal Stem Cell
摘要: 目的：通过生物信息学方法筛选强直性脊柱炎(AS)间充质干细胞核心基因并探讨其作用机制。方法：在GEO数据库中获取AS转录谱数据并使用R语言对其进行差异基因分析，再使用R软件对差异基因进行基因本体(GO)功能、京都基因与基因组百科全书(KEGG)富集分析，通过STRING在线数据库和Cytoscape软件来构建蛋白－蛋白相互作用(PPI)网络并筛选枢纽(Hub)基因，最后利用R软件对Hub基因的表达水平进行相关性分析。结果：经R软件DEG分析后得到101个差异基因(DEGs)，其中55个上调基因，46个下调基因。GO分析主要涉及多生物繁殖、多细胞生物过程，PiRNA代谢过程，免疫反应等。KEGG分析主要涉及PI3K-Akt信号通路。筛选出前10位Hub基因为ZIC1、EN1、TBX15、PITX2、PSG3、PSG4、PSG6、CPE、HOXC8、MAP2，它们之间的表达存在正相关。结论：DEGs和Hub基因可能在AS的发生发展中发挥着重要作用，主要与炎症反应，骨骼代谢，软骨细胞增殖分化等相关。
Abstract: Objective: This paper aims to screen the core genes of mesenchymal stem cells in ankylosing spon-dylitis (AS) by bioinformatics and explore its mechanism. Methods: The AS transcription profile da-ta were obtained from the GEO database and the differential gene analysis was performed using R language. The gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the differential genes were performed using R software. The protein-protein interaction (PPI) network was constructed by STRING online database and Cytoscape software, and the hub genes were screened. Finally, the correlation analysis of the expression level of Hub genes was performed using R software. Results: A total of 101 differentially expressed genes (DEGs) were obtained by R software DEG analysis, including 55 up-regulated genes and 46 down-regulated genes. GO analysis mainly involves multi-biological reproduction, multi-cellular biological processes, PiR-NA metabolic processes, immune responses, etc. KEGG analysis mainly involved the PI3K-Akt sig-naling pathway. The top 10 Hub genes were ZIC1, EN1, TBX15, PITX2, PSG3, PSG4, PSG6, CPE, HOXC8 and MAP2, and there was a positive correlation between their expression. Conclusion: DEGs and Hub genes may play an important role in the occurrence and development of AS, mainly related to inflammatory response, bone metabolism, chondrocyte proliferation and differentiation.
文章引用：叶天真, 李停. 强直性脊柱炎间充质干细胞差异基因的生物信息学分析[J]. 中医学, 2023, 12(10): 2859-2867. https://doi.org/10.12677/TCM.2023.1210429

参考文献

[1] 隋聪, 卜海富. 强直性脊柱炎发病机制与治疗的研究进展[J]. 临床骨科杂志, 2010, 13(2): 217-220.
[2] 谭希, 徐永跃, 邱冬妮, 等. 强直性脊柱炎动物模型归类及其机制研究与进展[J]. 中国组织工程研究, 2017, 21(11): 1783-1789.
[3] 李毓, 张强. 抗核抗体检测受试者核谱及核型特征分析[J]. 蚌埠医学院学报, 2022, 47(9): 1254-1258.
[4] 齐坤, 刘云, 唐滔, 等. 1,25(OH)2D3通过调节Th17/Treg比值和RANKL/OPG轴缓解胶原诱导的关节炎[J]. 陆军军医大学学报, 2023, 45(15): 1656-1665.
[5] 纵何香. RIOK3调控强直性脊柱炎成骨相关通路及骨髓间充质干细胞分化的潜在作用研究[D]: [博士学位论文]. 合肥: 安徽医科大学, 2023.
[6] 梁朝鑫, 周安远, 王伟, 等. 骨髓间充质干细胞治疗骨科疾病研究进展[J]. 陕西医学杂志, 2022, 51(1): 121-124, 129.
[7] 王嘉璐, 陈洪波. 益肾蠲痹丸联合理筋手法治疗强直性脊柱炎的病例报告及体会[J]. 湖北中医杂志, 2022, 44(8): 47-49.
[8] Abdolmohammadi, K., Pakdel, F.D., Aghaei, H., et al. (2019) Ankylosing Spondylitis and Mesenchymal Stromal/Stem Cell Therapy: A New Therapeutic Approach. Biomedicine & Pharmacotherapy, 109, 1196-1205. [Google Scholar] [CrossRef] [PubMed]
[9] Zeng, L., Yu, G., Yang, K., et al. (2022) Efficacy and Safety of Mesenchymal Stem Cell Transplantation in the Treatment of Autoimmune Diseases (Rheumatoid Arthritis, Systemic Lu-pus Erythematosus,Inflammatory Bowel Disease, Multiple Sclerosis, and Ankylosing Spondylitis): A Systematic Review and Meta-Analysis of Randomized Controlled Trial. Stem Cells International, 2022, Article 9463314. [Google Scholar] [CrossRef] [PubMed]
[10] 孔旭辉, 黄梁浒. 间充质干细胞调节炎症反应的研究进展[J]. 中华细胞与干细胞杂志(电子版), 2017, 7(6): 374-377.
[11] 梁大飞. MsPGN大鼠外周血Th17、Treg与炎症因子演变特征及PB-MSCs干预研究[D]: [硕士学位论文]. 遵义: 遵义医科大学, 2023.
[12] 燕春州. 大鼠骨髓间充质干细胞对LPS诱导的BV2细胞炎症反应的作用及机制研究[D]: [硕士学位论文]. 济宁: 济宁医学院, 2023.
[13] Shandil, R.K., Dhup, S. and Narayanan, S. (2022) Evaluation of the Therapeutic Potential of Mesenchymal Stem Cells (MSCs) in Preclinical Models of Autoimmune Diseases. Stem Cells International, 2022, Article 6379161. [Google Scholar] [CrossRef] [PubMed]
[14] Layh-Schmitt, G., Lu, S., Navid, F., et al. (2017) Generation and Dif-ferentiation of Induced Pluripotent Stem Cells Reveal Ankylosing Spondylitis Risk Gene Expression in Bone Progenitors. Clinical Rheumatology, 36, 143-154. [Google Scholar] [CrossRef] [PubMed]
[15] Fang, Y., Liu, J., Long, Y., et al. (2022) Knockdown of Circular RNA Hsa_Circ_0003307 Inhibits Synovial Inflammation in Ankylosing Spondylitis by Regulating the PI3K/AKT Path-way. Advances in Clinical and Experimental Medicine, 31, 781-788. [Google Scholar] [CrossRef] [PubMed]
[16] Liu, Z., Min, S., Lu, X., et al. (2022) [Hyperactivation of PI3K/AKT/mTOR Signal Pathway Impairs TNF-α-Induced Autophagy in Mesenchymal Stem Cells from Patients with Ankylosing Spondylitis]. Journal of Southern Medical University, 42, 272-277.
[17] Aruga, J. and Millen, K.J. (2018) ZIC1 Function in Normal Cerebellar Development and Human Developmental Pathology. In: Aruga, J., Eds., Zic Family, Springer, Singapore, 249-268. [Google Scholar] [CrossRef] [PubMed]
[18] Datta, H.K., Kringen, M.K., Tuck, S.P., et al. (2022) Mechanical-Stress-Related Epigenetic Regulation of ZIC1 Transcription Factor in the Etiology of Postmenopausal Osteoporosis. International Journal of Molecular Sciences, 23, Article 2957. [Google Scholar] [CrossRef] [PubMed]
[19] Kalogeropoulos, M., Varanasi, S.S., Olstad, O.K., et al. (2010) Zic1 Transcription Factor in Bone: Neural Developmental Protein Regulates Mechanotransduction in Osteocytes. The FASEB Journal, 24, 2893-2903. [Google Scholar] [CrossRef] [PubMed]
[20] Alves, D.S.M. and Smidt, M.P. (2011) En1 and Wnt Signaling in Mid-brain Dopaminergic Neuronal Development. Neural Development, 6, Article No. 23. [Google Scholar] [CrossRef] [PubMed]
[21] Eymard, F., Pigenet, A., Rose, C., et al. (2019) Contribution of Adi-pocyte Precursors in the Phenotypic Specificity of Intra-Articular Adipose Tissues in Knee Osteoarthritis Patients. Arthri-tis Research & Therapy, 21, Article No. 252. [Google Scholar] [CrossRef] [PubMed]
[22] Zheng, H.F., Forgetta, V., Hsu, Y.H., et al. (2015) Whole-Genome Sequencing Identifies EN1 as a Determinant of Bone Density and Fracture. Nature, 526, 112-117. [Google Scholar] [CrossRef] [PubMed]
[23] Hilton, T., Gross, M.K. and Kioussi, C. (2010) Pitx2-Dependent Occu-pancy by Histone Deacetylases Is Associated with T-Box Gene Regulation in Mammalian Abdominal Tissue. Journal of Biological Chemistry, 285, 11129-11142. [Google Scholar] [CrossRef] 
[24] Hashem, B.M., Hosseinpour, S.V., Maqbool, M., et al. (2022) Di-rectional Capacity of Human Mesenchymal Stem Cells to Support Hematopoietic Stem Cell Proliferation in vitro. Gene, 820, Article ID: 146218. [Google Scholar] [CrossRef] [PubMed]
[25] Fricker, L.D. (2018) Carboxypeptidase E and the Identification of Novel Neuropeptides as Potential Therapeutic Targets. Advances in Pharmacology, 82, 85-102. [Google Scholar] [CrossRef] [PubMed]
[26] Montzka, K., Lassonczyk, N., Tschöke, B., et al. (2009) Neural Differentiation Potential of Human Bone Marrow-Derived Mesenchymal Stromal Cells: Misleading Marker Gene Ex-pression. BMC Neuroscience, 10, Article No. 16. [Google Scholar] [CrossRef] [PubMed]