Regulatory role of CD177+ neutrophils in BMP signaling pathway and its implications for inflammatory bowel disease, sepsis, and intestinal tumors

IF 5 2区 医学 Q2 Medicine Translational Oncology Pub Date : 2025-03-29 DOI:10.1016/j.tranon.2025.102336
Lin Yu , Haoyue Zhang , Ling Jia , Detian Lai , Lina Jia , Qingzhu Li , Enwei Guo , Feng Yang , Bingyu Zhang , Qiancheng Luo
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Abstract

Objectives

Inflammatory bowel disease (IBD), sepsis, and intestinal tumors are major health threats. This study aimed to explore the regulatory role of CD177+ neutrophils in the BMP signaling pathway and its impact on the onset, progression, and treatment of these diseases.

Methods

Gene expression data from the Gene Expression Omnibus (GEO) database for IBD and sepsis were retrieved. Bioinformatics methods like background correction, normalization, and differential expression analysis were used. Weighted gene co-expression network analysis (WGCNA), gene functional enrichment analysis, pan-cancer analysis, single-cell analysis, and in vitro experiments including Caco-2 cell culture, cell proliferation assay (CCK-8), flow cytometry apoptosis analysis, quantitative real-time PCR (qRT-PCR), and plate colony formation assay were performed.

Results

Key genes associated with IBD and sepsis, such as BMP2, BMP4, BMP6, BMP8A, and CD177, were identified. WGCNA in sepsis found two significant modules related to key clinical outcomes. Core gene screening revealed seven shared genes between IBD and sepsis, and enrichment analysis showed involvement in important biological processes and pathways. Pan-cancer analysis showed diverse gene expression patterns and correlations with immune dynamics. Single-cell transcriptomics provided insights into the tumor microenvironment. In vitro experiments demonstrated that CD177 knockdown affected BMP signaling pathway-related gene expression, ROS production, apoptosis, and cell proliferation.

Conclusion

CD177+ neutrophils play a crucial role in regulating the BMP signaling pathway in IBD, sepsis, and intestinal tumors. These findings offer potential therapeutic targets, but further clinical validation is required to translate them into effective treatment strategies.

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CD177+ 中性粒细胞在 BMP 信号通路中的调节作用及其对炎症性肠病、败血症和肠肿瘤的影响
目的炎症性肠病(IBD)、败血症和肠道肿瘤是威胁人类健康的主要疾病。本研究旨在探讨 CD177+ 中性粒细胞在 BMP 信号通路中的调控作用及其对这些疾病的发生、发展和治疗的影响。方法从基因表达总库(GEO)数据库中检索 IBD 和败血症的基因表达数据。采用背景校正、归一化和差异表达分析等生物信息学方法。结果 发现了与 IBD 和败血症相关的关键基因,如 BMP2、BMP4、BMP6、BMP8A 和 CD177。败血症中的 WGCNA 发现了两个与关键临床结果相关的重要模块。核心基因筛选发现了 7 个 IBD 和败血症的共有基因,富集分析表明这些基因参与了重要的生物学过程和通路。泛癌症分析显示了不同的基因表达模式以及与免疫动态的相关性。单细胞转录组学揭示了肿瘤微环境。体外实验表明,CD177基因敲除会影响BMP信号通路相关基因的表达、ROS产生、细胞凋亡和细胞增殖。这些发现提供了潜在的治疗靶点,但要将其转化为有效的治疗策略还需要进一步的临床验证。
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来源期刊
CiteScore
8.40
自引率
2.00%
发文量
314
审稿时长
54 days
期刊介绍: Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.
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