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强直性脊柱炎骨髓间充质干细胞的全基因组表达谱分析及信号通路筛查

Whole Genome Expression Profiling and Signal Pathway Screening of MSCs in Ankylosing Spondylitis.

机构信息

Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 Yanjiang Road West, Guangzhou 510120, China.

Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 Yanjiang Road West, Guangzhou 510120, China.

出版信息

Stem Cells Int. 2014;2014:913050. doi: 10.1155/2014/913050. Epub 2014 Dec 3.

DOI:10.1155/2014/913050
PMID:25544849
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4269092/
Abstract

The pathogenesis of dysfunctional immunoregulation of mesenchymal stem cells (MSCs) in ankylosing spondylitis (AS) is thought to be a complex process that involves multiple genetic alterations. In this study, MSCs derived from both healthy donors and AS patients were cultured in normal media or media mimicking an inflammatory environment. Whole genome expression profiling analysis of 33,351 genes was performed and differentially expressed genes related to AS were analyzed by GO term analysis and KEGG pathway analysis. Our results showed that in normal media 676 genes were differentially expressed in AS, 354 upregulated and 322 downregulated, while in an inflammatory environment 1767 genes were differentially expressed in AS, 1230 upregulated and 537 downregulated. GO analysis showed that these genes were mainly related to cellular processes, physiological processes, biological regulation, regulation of biological processes, and binding. In addition, by KEGG pathway analysis, 14 key genes from the MAPK signaling and 8 key genes from the TLR signaling pathway were identified as differentially regulated. The results of qRT-PCR verified the expression variation of the 9 genes mentioned above. Our study found that in an inflammatory environment ankylosing spondylitis pathogenesis may be related to activation of the MAPK and TLR signaling pathways.

摘要

强直性脊柱炎（AS）中间充质干细胞（MSCs）功能失调的免疫调节机制的发病机制被认为是一个复杂的过程，涉及多个基因改变。在这项研究中，我们培养了来自健康供体和 AS 患者的 MSC，并在正常培养基或模拟炎症环境的培养基中进行培养。对 33351 个基因进行了全基因组表达谱分析，并通过 GO 术语分析和 KEGG 途径分析对与 AS 相关的差异表达基因进行了分析。我们的结果表明，在正常培养基中，AS 中有 676 个基因差异表达，其中 354 个上调，322 个下调，而在炎症环境中，AS 中有 1767 个基因差异表达，其中 1230 个上调，537 个下调。GO 分析表明，这些基因主要与细胞过程、生理过程、生物调节、生物过程调节和结合有关。此外，通过 KEGG 途径分析，我们确定了 MAPK 信号通路中的 14 个关键基因和 TLR 信号通路中的 8 个关键基因作为差异调节基因。qRT-PCR 的结果验证了上述 9 个基因的表达变化。我们的研究发现，在炎症环境中，强直性脊柱炎的发病机制可能与 MAPK 和 TLR 信号通路的激活有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fc/4269092/7b31b7354521/SCI2014-913050.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fc/4269092/0abfb16e2754/SCI2014-913050.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fc/4269092/76625694f968/SCI2014-913050.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fc/4269092/7b31b7354521/SCI2014-913050.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fc/4269092/0abfb16e2754/SCI2014-913050.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fc/4269092/76625694f968/SCI2014-913050.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fc/4269092/7b31b7354521/SCI2014-913050.003.jpg

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