Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
Mol Med Rep. 2017 Dec;16(6):8673-8684. doi: 10.3892/mmr.2017.7687. Epub 2017 Oct 2.
Acute gastric lesions induced by stress are frequent occurrences in medical establishments. The gastric dramatic downrelated gene (GDDR) is a secreted protein, which is abundantly expressed in normal gastric epithelia and is significantly decreased in gastric cancer. In our previous study, it was found that GDDR aggravated stress‑induced acute gastric lesions. However, the role of GDDR in acute gastric lesions remains to be fully elucidated. In the present study, RNA sequencing was performed in order to examine the gene expression profile regulated by GDDR in acute gastric lesions. The dataset comprised four stomach samples from wild-type (WT) mice and four stomach samples from GDDR‑knockout mice. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to analyze the differentially-expressed genes (DEGs). Weighted correlation network analysis was used to identify clusters of highly correlated genes. Cytoscape was used to construct a protein‑protein interaction network (PPI) of the DEGs. Based on the GO analysis, the upregulated DEGs were distinctly enriched in muscle contraction and response to wounding; and the downregulated DEGs were significantly enriched in the regulation of nitrogen compound metabolic process and regulation of RNA metabolic process. The results of the KEGG pathway analysis showed that the upregulated DEGs were enriched in ECM‑receptor interaction and the signaling pathway of cGMP‑PKG, and the downregulated DEGs were enriched in the renin‑angiotensin system and glycerolipid metabolism. The co‑expression network revealed a group of genes, which were associated with increased wound healing in the WT mice. Significant pathways were identified through the PPI network, including negative regulation of the signaling pathway of glucocorticoid receptor, regulation of cellular stress response, and regulation of hormone secretion. In conclusion, the present study improves current understanding of the molecular mechanism underlying acute gastric lesions and may assist in the treatment of gastric lesions.
应激引起的急性胃损伤在医疗机构中很常见。胃急剧下调基因(GDDR)是一种分泌蛋白,在正常胃上皮细胞中大量表达,在胃癌中显著降低。在我们之前的研究中,发现 GDDR 加重了应激诱导的急性胃损伤。然而,GDDR 在急性胃损伤中的作用仍有待充分阐明。本研究通过 RNA 测序来检测 GDDR 在急性胃损伤中调节的基因表达谱。数据集包括来自野生型(WT)小鼠的四个胃样本和来自 GDDR 敲除小鼠的四个胃样本。进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析以分析差异表达基因(DEGs)。加权相关网络分析用于识别高度相关基因的聚类。Cytoscape 用于构建 DEGs 的蛋白质-蛋白质相互作用网络(PPI)。基于 GO 分析,上调的 DEGs 明显富集在肌肉收缩和对创伤的反应中;而下调的 DEGs 则显著富集在氮化合物代谢过程的调节和 RNA 代谢过程的调节中。KEGG 通路分析的结果表明,上调的 DEGs 富集在 ECM-受体相互作用和 cGMP-PKG 的信号通路中,而下调的 DEGs 富集在肾素-血管紧张素系统和甘油磷脂代谢中。共表达网络揭示了一组与 WT 小鼠中伤口愈合增加相关的基因。通过 PPI 网络鉴定到显著通路,包括糖皮质激素受体信号通路的负调控、细胞应激反应的调节和激素分泌的调节。总之,本研究提高了对急性胃损伤分子机制的认识,可能有助于胃损伤的治疗。