Key pathway and gene alterations in the gastric mucosa associated with obesity and obesity-related diabetes
Key pathway and gene alterations in the gastric mucosa associated with obesity and obesity-related diabetes
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胃粘膜与肥胖和肥胖相关糖尿病相关的关键通路和基因改变
DOI：
10.1002/jcb.27976
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发表时间：
2019
影响因子：
4
通讯作者：
Qu Shen
中科院分区：
文献类型：
--
作者：
Wen Xin;Qian Chunhua;Zhang Yi;Wu Ruijin;Lu Liesheng;Zhu Cuiling;Cheng Xiaoyun;Cui Rai;You Hui;Mei Fangyun;Gao Jingyang;Li Feng;Bu Le;Qu Shen
背景与目的胃在肥胖及肥胖相关糖尿病中起重要作用；然而，我们对胃粘膜中与肥胖和糖尿病相关的关键通路知之甚少。方法采用基因芯片和实时聚合酶链反应（RT - PCR）对对照组（CON）、单纯性肥胖（OB）和肥胖合并糖尿病（OD）患者的肠道黏膜样本进行检测（每组3例）。使用基因本体（GO）和京都基因与基因组百科全书（KEGG）途径分析来预测差异表达基因的功能意义。结果与CON组相比，OB组共上调262个基因，下调265个基因，而OD组上调1756个基因，下调1053个基因。其中，23例在两种比较中均被共调控。7个差异表达基因（NRIP3、L1CAM、TPO、P2RY1、OR8A1、ADAMTS19和ASIC3）通过RT‐PCR验证。功能分析显示，OB组、OD组和CON组差异表达的基因在代谢、T细胞和G蛋白偶联受体生物学过程中发挥重要作用，主要参与PI3K‐Akt和AGE‐RAGE信号通路。结论肥胖及肥胖相关糖尿病与胃重要基因表达及通路改变有关。
Background and ObjectiveThe stomach plays an important role in obesity and obesity‐related diabetes; yet, little is known about key pathways in the gastric mucosa associated with obesity and diabetes.MethodsWe performed gene microarray and real time‐polymerase chain reaction (RT‐PCR) on gut mucosa samples from control subjects (CON), patients with simple obesity (OB), and patients with obesity and comorbid diabetes (OD) (n = 3 per group). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to predict the functional significance of differentially expressed genes.ResultsIn total, 262 genes were upregulated and 265 genes were downregulated in the OB group whereas 1756 genes were upregulated and 1053 genes were downregulated in the OD group compared with the CON group. Of these, 23 were co‐regulated in both comparisons. Seven differentially expressed genes were validated by RT‐PCR (NRIP3, L1CAM, TPO, P2RY1, OR8A1, ADAMTS19, and ASIC3). A functional analysis revealed that genes differentially expressed between the OB or OD and CON groups played crucial roles in metabolic, T cell, and G‐protein coupled receptor biological processes, and primarily participated in the PI3K‐Akt and AGE‐RAGE signaling pathways.ConclusionsObesity and obesity‐related diabetes are associated with important gene expression and pathway alterations in the stomach.