Song Ruifeng, Li Ya, Hao Weiwei, Wang Bingxue, Yang Lei, Xu Feng
Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Medicine (Baltimore). 2018 May;97(21):e10658. doi: 10.1097/MD.0000000000010658.
This study aimed to identify genes that may play a role in development of ulcerative colitis (UC) and gain insight into its pathogenesis.Gene expression profiling data, including samples collected from 13 early-stage UC (EUC), 8 advanced-stage UC (AUC), and 5 control subjects, were downloaded from the Gene Expression Omnibus database under the accession number of GSE9452. Differentially expressed genes (DEGs) were identified in EUC and AUC compared with controls. DEGs for EUC and AUC, as well as AUC-specific DEGs were subjected to pathway enrichment analysis. Random Walk with Restart (RWR) was used to identify DEGs that are critical in UC based on a protein-to-protein interaction (PPI) network and the inflammatory bowel disease (IBD) pathway downloaded from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. IL17 and transforming growth factor beta TGF-β) expression levels in colonic tissue from patients with UC and normal colonic mucosa from healthy adults were analyzed by immunohistochemistry (IHC).A total of 3511 and 911 DEGs were identified in AUC and EUC, respectively. The overlapping DEGs and the AUC-specific DEGs were both enriched in pathways related to immunity, such as antigen processing and presentation. AUC-specific DEGs were related to cell migration, such as ECM-receptor interaction. Following DEG prioritization, TLR4 and STAT1 were linked with EUC, AUC, and CD. The upregulated gene TGFB increased the number of Th17 cells, as verified by IHC. Furthermore, PIK3R1, CREBBP, and STAT1 were part of high-degree nodes in the PPI sub-network.The upregulated gene TGFB may regulate IL17 expression in UC. PIK3R1 may participate in immunity and CREBBP may interact with STAT1 in the development and progression of UC.
本研究旨在鉴定可能在溃疡性结肠炎（UC）发病过程中起作用的基因，并深入了解其发病机制。从基因表达综合数据库下载了基因表达谱数据，包括从13例早期UC（EUC）、8例晚期UC（AUC）和5例对照受试者采集的样本，登录号为GSE9452。与对照组相比，在EUC和AUC中鉴定出差异表达基因（DEG）。对EUC和AUC的DEG以及AUC特异性DEG进行通路富集分析。基于从京都基因与基因组百科全书（KEGG）数据库下载的蛋白质-蛋白质相互作用（PPI）网络和炎症性肠病（IBD）通路，使用带重启的随机游走（RWR）来鉴定在UC中起关键作用的DEG。通过免疫组织化学（IHC）分析UC患者结肠组织和健康成年人正常结肠黏膜中白细胞介素17（IL17）和转化生长因子β（TGF-β）的表达水平。在AUC和EUC中分别鉴定出3511个和911个DEG。重叠的DEG和AUC特异性DEG均富集于与免疫相关的通路，如抗原加工和呈递。AUC特异性DEG与细胞迁移相关，如细胞外基质-受体相互作用。在对DEG进行优先级排序后，Toll样受体4（TLR4）和信号转导和转录激活因子1（STAT1）与EUC、AUC和克罗恩病（CD）相关。免疫组织化学证实，上调基因TGFB增加了辅助性T细胞17（Th17）细胞的数量。此外，磷脂酰肌醇-3激酶调节亚基1（PIK3R1）、CREB结合蛋白（CREBBP）和STAT1是PPI子网中高度节点的一部分。上调基因TGFB可能在UC中调节IL17的表达。PIK3R1可能参与免疫，CREBBP可能在UC的发生和发展过程中与STAT1相互作用。
