Dipeptidyl peptidase 4: A predictor of ferroptosis in ulcerative colitis

IF 3.2 4区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of Gene Medicine Pub Date : 2024-09-29 DOI:10.1002/jgm.3742

Fuyun Zhu, Dezeng Zou, Ping Shi, Lianhua Tang, Dan Wu, Xiaoxue Hu, Fei Yin, Jianhui Liu

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引用次数: 0

Abstract

Background

With its rapidly increasing incidence and prevalence, ulcerative colitis (UC) has become a major global health challenge. Recent evidence suggests that ferroptosis plays a significant role in the development of UC. However, the relationship between ferroptosis and the progression of UC needs to be extensively studied.

Methods

The differentially expressed genes in UC patients were screened from the GEO database. The ferroptosis-related genes were obtained from FErrDB and GeneCards. The UC subtypes were identified with the R package “CancerSubtype” and evaluated with consensus clustering (CC) to identify gene expression patterns in patients with UC. The key genes were detected with qRT-PCR, Western blot, and immunohistochemistry in vitro and in vivo models. Ferroptosis was identified with western blotting on ferrotic-associated proteins and staining on Fe²⁺ with commercial FerroOrange kits.

Results

Dipeptidyl peptidase 4 (DPP4), also known as CD26, is a potential biomarker for ferroptosis in UC patients. Transcriptome sequencing data showed a positive correlation between decreased DPP4 expression and proinflammatory cytokines such as TNF-α, IL-6, and IL-β, as well as immune cell infiltration in the colon tissues of UC patients. Furthermore, DPP4 was strongly associated with ferroptosis biomarkers, particularly in Subtype 2 of UC. Interestingly, our study also found that DPP4 expression was significantly reduced in RSL3-treated ferroptotic intestinal epithelial cells, more so than in LPS-treated cell models. Inhibition of DPP4 had a significant impact on the expression of ferroptotic biomarkers. Additionally, DPP4 expression was decreased in the colon tissues of DSS-treated mice, and the ferroptosis inhibitor Ferritin-1 effectively counteracted the effects of DSS on immune cell infiltration, colon length, and DPP4 expression.

Conclusions

DPP4 can serve as a biomarker for ferroptosis in the diagnosis and management of UC.

Abstract Image

查看原文本刊更多论文

二肽基肽酶 4：溃疡性结肠炎铁质沉积症的预测因子。

背景：溃疡性结肠炎（UC）的发病率和流行率迅速上升，已成为全球健康面临的一大挑战。最近的证据表明，高铁血症在溃疡性结肠炎的发展中起着重要作用。然而，铁变态反应与溃疡性结肠炎进展之间的关系仍有待广泛研究：方法：从 GEO 数据库中筛选出 UC 患者的差异表达基因。方法：从 GEO 数据库中筛选出 UC 患者中差异表达的基因，并从 FErrDB 和 GeneCards 中获得铁变态反应相关基因。用 R 软件包 "CancerSubtype "确定 UC 亚型，并用共识聚类（CC）进行评估，以确定 UC 患者的基因表达模式。通过 qRT-PCR、Western 印迹和免疫组化技术检测了体外和体内模型中的关键基因。通过对铁质相关蛋白进行Western印迹，并使用商业FerroOrange试剂盒对Fe2+进行染色，确定了铁质沉着：结果：二肽基肽酶 4 (DPP4)，又称 CD26，是 UC 患者铁变态反应的潜在生物标志物。转录组测序数据显示，DPP4表达量减少与TNF-α、IL-6和IL-β等促炎细胞因子以及UC患者结肠组织中的免疫细胞浸润呈正相关。此外，DPP4 与铁变态反应生物标志物密切相关，尤其是在亚型 2 UC 中。有趣的是，我们的研究还发现，在 RSL3 处理的铁败血症肠上皮细胞中，DPP4 的表达明显减少，比在 LPS 处理的细胞模型中更明显。抑制 DPP4 对铁变态反应生物标志物的表达有重大影响。此外，经 DSS 处理的小鼠结肠组织中 DPP4 的表达量减少，而铁变态反应抑制剂铁蛋白-1 能有效抵消 DSS 对免疫细胞浸润、结肠长度和 DPP4 表达量的影响：结论：DPP4可作为诊断和治疗UC的铁变态反应生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Gene Medicine 医学-生物工程与应用微生物

CiteScore

6.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.