Zhu Huatuo, Wan Xingyong, Li Jing, Han Lu, Bo Xiaochen, Chen Wenguo, Lu Chao, Shen Zhe, Xu Chenfu, Chen Lihua, Yu Chaohui, Xu Guoqiang
Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Department of Gastroenterology, Peking University People's Hospital, Beijing, China.
Sci Rep. 2015 Jul 17;5:12227. doi: 10.1038/srep12227.
Ulcerative colitis (UC) is a common inflammatory bowel disease (IBD) producing intestinal inflammation and tissue damage. The precise aetiology of UC remains unknown. In this study, we applied a rank-based expression profile comparative algorithm, gene set enrichment analysis (GSEA), to evaluate the expression profiles of UC patients and small interfering RNA (siRNA)-perturbed cells to predict proteins that might be essential in UC from publicly available expression profiles. We used quantitative PCR (qPCR) to characterize the expression levels of those genes predicted to be the most important for UC in dextran sodium sulphate (DSS)-induced colitic mice. We found that bromo-adjacent homology domain (BAHD1), a novel heterochromatinization factor in vertebrates, was the most downregulated gene. We further validated a potential role of BAHD1 as a regulatory factor for inflammation through the TNF signalling pathway in vitro. Our findings indicate that computational approaches leveraging public gene expression data can be used to infer potential genes or proteins for diseases, and BAHD1 might act as an indispensable factor in regulating the cellular inflammatory response in UC.
溃疡性结肠炎(UC)是一种常见的炎症性肠病(IBD),可导致肠道炎症和组织损伤。UC的确切病因尚不清楚。在本研究中,我们应用了一种基于秩次的表达谱比较算法——基因集富集分析(GSEA),通过公开的表达谱评估UC患者和小干扰RNA(siRNA)干扰细胞的表达谱,以预测可能在UC中起关键作用的蛋白质。我们使用定量聚合酶链反应(qPCR)来表征在葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠中那些预测对UC最重要的基因的表达水平。我们发现,脊椎动物中的一种新型异染色质化因子——溴邻同源结构域1(BAHD1)是下调最明显的基因。我们进一步在体外验证了BAHD1作为通过肿瘤坏死因子(TNF)信号通路调节炎症的潜在作用。我们的研究结果表明,利用公共基因表达数据的计算方法可用于推断疾病的潜在基因或蛋白质,并且BAHD1可能是调节UC细胞炎症反应的不可或缺的因素。
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