基于实验研究和生物信息学筛选三种小鼠肺疾病的炎症相关关键基因

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摘要 目的: 应用RNA测序和生物信息学方法筛选小鼠矽肺、特发性肺纤维化（idiopathic pulmonary fibrosis,IPF）和慢性阻塞性肺部疾病（chronic obstructive pulmonary diseases,COPD）共同枢纽基因,以期为这三种肺部疾病的诊断和治疗提供新的实验依据。方法: 建立小鼠矽肺模型并验证,提取矽肺小鼠肺组织进行RNA测序。采用limma 包筛选差异表达基因（differentially expressed genes,DEGs）,采用ggplot包绘制火山图;采用韦恩图筛选小鼠矽肺与IPF 、COPD的共有DEGs;通过STRING 数据库构建蛋白质–蛋白质相互作用（protein-protein interactions,PPI）网络识别DEGs中的关键基因;关键基因在矽肺、IPF和COPD小鼠中的表达水平通过qPCR和GEO数据集进行验证。结果: 通过构建小鼠矽肺模型和小鼠肺组织RNA测序,结合IPF和COPD小鼠数据集,三种疾病共鉴定出8个共同的DEGs;qPCR结果显示,Cxcl10、MMP12、Lcn2在矽肺小鼠肺组织中显著增加,而Ctss水平无显著变化;在IPF和COPD的验证集中,Ctss、Cxcl10、MMP12、Lcn2均呈现高表达。结论: Cxcl10、MMP12、Lcn2是小鼠矽肺、IPF和COPD潜在的炎症相关关键基因。

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	王汉钦
	康慧敏
	周珂
	李柔
	陈适

关键词 ：矽肺病, 特发性肺纤维化, 慢性阻塞性肺部疾病, 炎症, 关键基因

Abstract：Objective RNA sequencing and bioinformatics methods were utilized to identify key genes associated with mouse silicosis, idiopathic pulmonary fibrosis (IPF), and chronic obstructive pulmonary disease (COPD). This research aims to establish a novel experimental foundation for diagnosing and treating chronic inflammatory lung diseases. Methods A mouse model of silicosis was established and validated, then RNA sequencing was conducted on the lung tissues of silicosis mice. Differentially expressed genes (DEGs) were identified using the limma package, volcano and heat maps were generated with the ggplot package. Common DEGs in silicosis, IPF, and COPD were identified using a Venn diagram. A protein-protein interaction (PPI) network was constructed using the STRING database to identify key genes among the DEGs. The expression of key genes in the lung tissues of silicosis mice was validated through qPCR assays, and the expression of key genes in IPF and COPD mice was validated using the GSE218997 and GSE76205 datasets. Results A mouse silicosis model was established and RNA sequencing of mouse lung tissue was performed, in conjunction with datasets from IPF and COPD mice, a total of 8 common DEGs were identified across the three diseases. The qPCR results revealed a significant increase in Cxcl10, MMP12, and Lcn2 in the lung tissue of silicosis mice, while no significant change was observed in Ctss levels. In the validation sets of IPF and COPD, Ctss, Cxcl10, MMP12, and Lcn2 all showed high expression. Conclusion Cxcl10, MMP12, and Lcn2 are potential inflammation related key genes for mouse silicosis, IPF, and COPD.

Key words： silicosis idiopathic pulmonary fibrosis chronic obstructive pulmonary diseases inflammation key gene

收稿日期: 2023-12-21

中图分类号:	R563
	R363

基金资助:国家自然科学基金“TLR4-TRAF6-Beclin1 信号轴调控p62介导的肺泡巨噬细胞自噬对矽肺纤维化的作用机制研究”（82173493）; 湖南省自然科学基金“Galunisertib通过TGF-β信号通路对小鼠矽肺纤维化的作用研究”（2023JJ30423）

通讯作者: 陈适,E-mail：chenshonest@163.com

引用本文:

王汉钦, 康慧敏, 周珂, 李柔, 陈适. 基于实验研究和生物信息学筛选三种小鼠肺疾病的炎症相关关键基因[J]. 湖南师范大学学报(医学版), 2024, 21(2): 21-26. WANG Hanqin, KANG Huimin, ZHOU Ke, LI Rou, CHEN Shi. Identification of inflammation related key genes in three mouse lung diseases based on experimental studies and bioinformatics. HuNan ShiFan DaXue XueBao(YiXueBan), 2024, 21(2): 21-26.

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http://yxb.hunnu.edu.cn/CN/ 或 http://yxb.hunnu.edu.cn/CN/Y2024/V21/I2/21

[1] LEUNG C C, YU I T, CHEN W.Silicosis[J]. Lancet, 2012, 379(9830): 2008-2018.
[2] PODOLANCZUK A J, THOMSON C C, REMY-JARDIN M, et al.Idiopathic pulmonary fibrosis: state of the art for 2023[J]. Eur Respir J, 2023, 61(4): 2200957.
[3] CHRISTENSON S A, SMITH B M, BAFADHEL M, et al.Chronic obstructive pulmonary disease[J]. Lancet, 2022, 399(10342): 2227-2242.
[4] ZHAO Q, FAN Y L, MA R M, et al.Prevalence and risk factors of silicosis complicated with chronic obstructive pulmonary disease[J]. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi, 2022, 40(8): 602-606.
[5] WALTERS G I.Occupational exposures and idiopathic pulmonary fibrosis[J]. Curr Opin Allergy Clin Immunol, 2020, 20(2): 103-111.
[6] MA P, LI S, YANG H, et al.Comparative RNA-Seq Transcriptome Analysis on Pulmonary Inflammation in a Mouse Model of Asthma-COPD Overlap Syndrome[J]. Front Cell Dev Biol, 2021, 9: 628957.
[7] CĂLU U I M, SMĂRĂNDESCU R A, RA CU A. Biomonitoring Exposure and Early Diagnosis in Silicosis: A Comprehensive Review of the Current Literature[J]. Biomedicines, 2022, 11(1): 100.
[8] HUANG G, XU X, JU C, et al.Identification and validation of autophagy-related gene expression for predicting prognosis in patients with idiopathic pulmonary fibrosis[J]. Front Immunol, 2022, 13: 997138.
[9] ZHANG Y, XIA R, LV M, et al.Machine-Learning Algorithm-Based Prediction of Diagnostic Gene Biomarkers Related to Immune Infiltration in Patients With Chronic Obstructive Pulmonary Disease[J]. Front Immunol, 2022, 13: 740513.
[10] ROMAN J, MUTSAERS S E.Epigenetic Control of CXCL10: Regulating the Counterregulator in Idiopathic Pulmonary Fibrosis[J]. Am J Respir Cell Mol Biol, 2018, 58(4): 419-420.
[11] ZHOU C, GAO Y, DING P, et al.The role of CXCL family members in different diseases[J]. Cell Death Discov, 2023, 9(1): 212.
[12] SU L, DONG Y, WANG Y, et al.Potential role of senescent macrophages in radiation-induced pulmonary fibrosis[J]. Cell Death Dis, 2021, 12(6): 527.
[13] GUI X, QIU X, TIAN Y, et al.Prognostic value of IFN-γ, sCD163, CCL2 and CXCL10 involved in acute exacerbation of idiopathic pulmonary fibrosis[J]. Int Immunopharmacol, 2019, 70: 208-215.
[14] KAMEDA M, OTSUKA M, CHIBA H, et al.CXCL9, CXCL10, and CXCL11; biomarkers of pulmonary inflammation associated with autoimmunity in patients with collagen vascular diseases-associated interstitial lung disease and interstitial pneumonia with autoimmune features[J]. PLoS One, 2020, 15(11): e0241719.
[15] BENMERZOUG S, ROSE S, BOUNAB B, et al.STING-dependent sensing of self-DNA drives silica-induced lung inflammation[J]. Nat Commun, 2018, 9(1): 5226.
[16] 唐乐婷, 曹卜子, 于浩. 基于综合生物信息学对睾丸生殖细胞肿瘤预后相关枢纽基因的筛选及验证[J]. 湖南师范大学学报 (医学版), 2022, 19(03): 196-201.
[17] GHARIB S A, MANICONE A M, PARKS W C.Matrix metalloproteinases in emphysema[J]. Matrix Biol, 2018, 73: 34-51.
[18] TAKIMOTO-SATO M, SUZUKI M, KIMURA H, et al.Apoptosis inhibitor of macrophage (AIM) /CD5L is involved in the pathogenesis of COPD[J]. Respir Res, 2023, 24(1): 201.
[19] BAGGIO C, VELAZQUEZ J V, FRAGAI M, et al.Therapeutic Targeting of MMP-12 for the Treatment of Chronic Obstructive Pulmonary Disease[J]. J Med Chem, 2020, 63(21): 12911-12920.
[20] GENG F, XU M, ZHAO L, et al.Quercetin Alleviates Pulmonary Fibrosis in Mice Exposed to Silica by Inhibiting Macrophage Senescence[J]. Front Pharmacol, 2022, 13: 912029.
[21] ZHOU X, ZHANG C, YANG S, et al.Macrophage-derived MMP12 promotes fibrosis through sustained damage to endothelial cells[J]. J Hazard Mater, 2024, 461: 132733.
[22] CRAIG V J, ZHANG L, HAGOOD J S, et al.Matrix metalloproteinases as therapeutic targets for idiopathic pulmonary fibrosis[J]. Am J Respir Cell Mol Biol, 2015, 53(5): 585-600.
[23] AN H S, YOO J W, JEONG J H, et al.Lipocalin-2 promotes acute lung inflammation and oxidative stress by enhancing macrophage iron accumulation[J]. Int J Biol Sci, 2023, 19(4): 1163-1177.
[24] WANG X, ZHANG C, ZOU N, et al.Lipocalin-2 silencing suppresses inflammation and oxidative stress of acute respiratory distress syndrome by ferroptosis via inhibition of MAPK/ERK pathway in neonatal mice[J]. Bioengineered, 2022, 13(1): 508-520.
[25] TREEKITKARNMONGKOL W, HASSANE M, SINJAB A, et al.Augmented Lipocalin-2 Is Associated with Chronic Obstructive Pulmonary Disease and Counteracts Lung Adenocarcinoma Development[J]. Am J Respir Crit Care Med, 2021, 203(1): 90-101.
[26] GALARIS A, FANIDIS D, TSITOURA E, et al.Increased lipocalin-2 expression in pulmonary inflammation and fibrosis[J]. Front Med (Lausanne), 2023, 10: 1195501.
[27] BO C, ZHANG J, SAI L, et al.Integrative transcriptomic and proteomic analysis reveals mechanisms of silica-induced pulmonary fibrosis in rats[J]. BMC Pulm Med, 2022, 22(1): 13.
[28] GUPTA U, GHOSH S, WALLACE C T, et al.Increased LCN2(lipocalin 2) in the RPE decreases autophagy and activates inflammasome-ferroptosis processes in a mouse model of dry AMD[J]. Autophagy, 2023, 19(1): 92-111.