中国临床药理学杂志

基于人源原代肺成纤维细胞转录组学筛选放射性肺损伤治疗靶点的研究

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罗鑫 ¹^,² , 李九龙 ³ , 陈瑜 ¹^,² , 王哲 ² , 邱志维 ² , 向倩 ² , 孟幻 ³ , 崔一民 ¹^,²

中国临床药理学杂志 | 读者园地 2026,42(4): 535-540

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中国临床药理学杂志 |读者园地 2026 , 42 (4) : 535 -540

基于人源原代肺成纤维细胞转录组学筛选放射性肺损伤治疗靶点的研究

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罗鑫¹^,², 李九龙³, 陈瑜¹^,², 王哲², 邱志维², 向倩², 孟幻³, 崔一民¹^,²

作者信息

^1.温州医科大学药学院，浙江温州 325035

^2.北京大学第一医院临床药理研究所，北京 100034

^3.中国科学院国家纳米科学中心，北京 100190

通讯作者:

崔一民，教授，博士生导师 Tel: （010）83573729 E-mail: cui.pharm@pkufh.com

作者简介:

罗鑫（2000-），女，硕士研究生，主要从事临床药学方面的工作和研究

Research of screening of therapeutic targets for radiation-induced lung injury based on transcriptomics of human primary lung fibroblasts

Xin LUO¹^,², Jiu-long LI³, Yu CHEN¹^,², Zhe WANG², Zhi-wei QIU², Qian XIANG², Huan MENG³, Yi-min CUI¹^,²

Affiliations

^1.School of Pharmacy, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China

^2.Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100034, China

^3.National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing 100190, China

出版时间: 2026-02-28 doi: 10.13699/j.cnki.1001-6821.2026.04.013

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摘要

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目的

建立人肺原代成纤维细胞放射性损伤模型，通过转录组学测序筛选驱动放射性肺纤维化的关键基因，并阐明其潜在的作用机制，为临床防治放疗诱导的肺损伤提供新的治疗靶点与策略。

方法

通过胶原酶法分离人肺组织原代成纤维细胞并进行传代培养，经流式细胞术鉴定细胞纯度后，建立体外放射性辐照模型，并依据测序数据质量评估结果进行转录组分析。通过DESeq2进行差异表达分析，筛选出上调差异基因并进行验证。通过String数据库预测分组差异基因集蛋白之间联系，并用igraph包构建蛋白网络互作图。最终，用clusterProfiler软件，通过基因本体（GO）、京都基因与基因组百科全书（KEGG）和基因集富集分析（GSEA）分析方法，对筛选的核心基因进行功能与通路分析。

结果

样本质量合格，转录组分析筛选出显著上调的3个关键差异基因，分别是硫酸酯酶1（SULF1）、硫酸酯酶2（SULF2）和少突胶质细胞髓磷脂糖蛋白（OMG），相同的结果在公共验证集中得到一致性证实。通过Cytoscape进行蛋白质互作（PPI）分析，结果显示SULF1处于网络的核心位置，与SULF2连接紧密，且二者均与OMG存在直接相互作用。GSEA富集分析显示，SULF1/2、OMG显著富集于DNA功能相关、谷胱甘肽转移酶活性及神经免疫调控等相关通路。SULF1/2、OMG可能通过参与DNA损伤、氧化应激及神经免疫交互调控等途径，在辐射诱导放射性肺损伤中发挥作用。

结论

SULF1/2、OMG是人肺成纤维细胞响应辐射损伤的关键分子，可能通过多种途径驱动放射性肺损伤进程，作为潜在的干预靶点，可为临床防治放疗诱导的肺损伤提供新的理论依据。

关键词

放射性肺损伤 / 人肺原代成纤维细胞 / 转录组测序 / 信号通路

Abstract

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Objective

To establish a radiation injury model using primary human lung fibroblasts and screen for key genes driving radiation-induced pulmonary fibrosis through transcriptome sequencing, thereby elucidating their potential mechanisms and providing new therapeutic targets and strategies for the clinical prevention and treatment of radiotherapy-induced lung injury.

Methods

Primary human lung fibroblasts were isolated by collagenase digestion and serially passaged. Cell purity was confirmed by flow cytometry prior to establishing an in vitro radiation model. Transcriptome analysis was performed based on qualified sequencing data. DESeq2 was used for differential expression analysis to identify upregulated genes, which were subsequently validated. Protein-protein interactions (PPI) among the differentially expressed gene sets were predicted using the String database and visualized using the igraph package. Finally, functional and pathway enrichment analyses of the core genes were performed via gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA) using the clusterProfiler software.

Results

All samples met the quality control standards. Transcriptome analysis identified three significantly upregulated key differentially expressed genes: sulfatase 1 (SULF1), sulfatase 2 (SULF2), and oligodendrocyte myelin glycoprotein (OMG). These findings were consistently validated in a public dataset. PPI network analysis constructed with Cytoscape revealed that SULF1 occupied a central hub position within the network, exhibiting a strong connection with SULF2, and both directly interacted with OMG. GSEA indicated that SULF1/2 and OMG were significantly enriched in pathways related to DNA function, glutathione transferase activity, and neuroimmune regulation. These results suggested that SULF1/2 and OMG may function in radiation-induced lung injury by participating in processes such as DNA damage response, oxidative stress, and neuroimmune interactions.

Conclusion

SULF1, SULF2 and OMG are key molecules in human lung fibroblasts responding to radiation injury and may drive the progression of radiation-induced lung injury through multiple pathways. As potential therapeutic targets, they provide a novel theoretical basis for the clinical prevention and treatment of radiotherapy-induced lung injury.

Key words

radiation-induced lung injury / primary human lung fibroblasts / transcriptome sequencing / signaling pathway

引用本文

罗鑫, 李九龙, 陈瑜, 王哲, 邱志维, 向倩, 孟幻, 崔一民. 基于人源原代肺成纤维细胞转录组学筛选放射性肺损伤治疗靶点的研究. 中国临床药理学杂志, 2026 , 42 (4) : 535 -540 . DOI: 10.13699/j.cnki.1001-6821.2026.04.013

Xin LUO, Jiu-long LI, Yu CHEN, Zhe WANG, Zhi-wei QIU, Qian XIANG, Huan MENG, Yi-min CUI. Research of screening of therapeutic targets for radiation-induced lung injury based on transcriptomics of human primary lung fibroblasts[J]. Chinese Journal of Clinical Pharmacology, 2026 , 42 (4) : 535 -540 . DOI: 10.13699/j.cnki.1001-6821.2026.04.013

基金

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国家自然科学基金资助项目(82274024)

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2026年第42卷第4期

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文章信息

doi: 10.13699/j.cnki.1001-6821.2026.04.013

接收时间：2026-01-29
首发时间：2026-08-06
出版时间：2026-02-28

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收稿日期：2026-01-29

基金

国家自然科学基金资助项目(82274024)

作者信息

^1.温州医科大学药学院，浙江温州 325035

^2.北京大学第一医院临床药理研究所，北京 100034

^3.中国科学院国家纳米科学中心，北京 100190

通讯作者:

崔一民，教授，博士生导师 Tel: （010）83573729 E-mail: cui.pharm@pkufh.com

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https://castjournals.cast.org.cn/joweb/zglcylxzz/CN/10.13699/j.cnki.1001-6821.2026.04.013

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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