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通过综合生物信息学分析和体外分析鉴定与急性胰腺炎和慢性胰腺炎相关的潜在枢纽基因

Identification of Potential Hub Genes Related to Acute Pancreatitis and Chronic Pancreatitis via Integrated Bioinformatics Analysis and In Vitro Analysis.

作者信息

Yuan Lu, Liu Yiyuan, Fan Lingyan, Sun Cai, Ran Sha, Huang Kuilong, Shen Yan

机构信息

School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, 400054, China.

Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Medical Group), Qingdao, 266042, China.

出版信息

Mol Biotechnol. 2025 Mar;67(3):1188-1200. doi: 10.1007/s12033-024-01118-5. Epub 2024 Mar 23.

Abstract

Acute pancreatitis (AP) and chronic pancreatitis (CP) are considered to be two separate pancreatic diseases in most studies, but some clinical retrospective analyses in recent years have found some degree of correlation between the two in actual treatment, however, the exact association is not clear. In this study, bioinformatics analysis was utilized to examine microarray sequencing data in mice, with the aim of elucidating the critical signaling pathways and genes involved in the progression from AP to CP. Differential gene expression analyses on murine transcriptomes were conducted using the R programming language and the R/Bioconductor package. Additionally, gene network analysis was performed using the STRING database to predict correlations among genes in the context of pancreatic diseases. Functional enrichment and gene ontology pathways common to both diseases were identified using Metascape. The hub genes were screened in the cytoscape algorithm, and the mRNA levels of the hub genes were verified in mice pancreatic tissues of AP and CP. Then the drugs corresponding to the hub genes were obtained in the drug-gene relationship. A set of hub genes, including Jun, Cd44, Epcam, Spp1, Anxa2, Hsp90aa1, and Cd9, were identified through analysis, demonstrating their pivotal roles in the progression from AP to CP. Notably, these genes were found to be enriched in the Helper T-cell factor (Th17) signaling pathway. Up-regulation of these genes in both AP and CP mouse models was validated through quantitative real-time polymerase chain reaction (qRT-PCR) results. The significance of the Th17 signaling pathway in the transition from AP to CP was underscored by our findings. Specifically, the essential genes driving this progression were identified as Jun, Cd44, Epcam, Spp1, Anxa2, Hsp90aa1, and Cd9. Crucial insights into the molecular mechanisms underlying pancreatitis progression were provided by this research, offering promising avenues for the development of targeted therapeutic interventions.

摘要

在大多数研究中,急性胰腺炎(AP)和慢性胰腺炎(CP)被认为是两种不同的胰腺疾病,但近年来一些临床回顾性分析发现,在实际治疗中两者存在一定程度的相关性,然而,确切的关联尚不清楚。在本研究中,利用生物信息学分析来检查小鼠的微阵列测序数据,目的是阐明从AP进展到CP所涉及的关键信号通路和基因。使用R编程语言和R/Bioconductor软件包对小鼠转录组进行差异基因表达分析。此外,使用STRING数据库进行基因网络分析,以预测胰腺疾病背景下基因之间的相关性。使用Metascape识别两种疾病共有的功能富集和基因本体途径。在Cytoscape算法中筛选枢纽基因,并在AP和CP小鼠胰腺组织中验证枢纽基因的mRNA水平。然后在药物-基因关系中获得与枢纽基因对应的药物。通过分析确定了一组枢纽基因,包括Jun、Cd44、Epcam、Spp1、Anxa2、Hsp90aa1和Cd9,证明它们在从AP进展到CP过程中起关键作用。值得注意的是,这些基因在辅助性T细胞因子(Th17)信号通路中富集。通过定量实时聚合酶链反应(qRT-PCR)结果验证了这些基因在AP和CP小鼠模型中的上调。我们的研究结果强调了Th17信号通路在从AP转变为CP中的重要性。具体而言,驱动这一进展的关键基因被确定为Jun、Cd44、Epcam、Spp1、Anxa2、Hsp90aa1和Cd9。这项研究为胰腺炎进展的分子机制提供了关键见解,为开发靶向治疗干预措施提供了有希望的途径。

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