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CFH基因在特发性肺纤维化中的新角色:验证与功能研究
作者:史宁1  乃菲沙·买买提1  王亮2  尚晓倩1  孙玉钦1  周金萍1  陈佳慧1  李佳峻1  王晶3 4  马秀敏1 
单位:1. 新疆医科大学附属肿瘤医院 医学检验中心, 省部共建中亚高发病成因与防治国家重点实验室, 新疆 乌鲁木齐 830011;
2. 新疆医科大学 第五附属医院, 新疆 乌鲁木齐 830011;
3. 海南医科大学 第二附属医院, 海南 海口 570100;
4. 新疆医科大学 第一附属医院, 新疆 乌
关键词:补体因子H 特发性肺纤维化 基因表达差异分析 生物标志物 蛋白质-蛋白质相互作用 
分类号:R563
出版年·卷·期(页码):2024·43·第三期(346-355)
摘要:

目的:探讨特发性肺纤维化(IPF)治疗的新途径。方法:通过生物信息学算法来探索与IPF进展相关的共同表达基因和生物途径。应用加权基因共表达网络分析(WGCNA)识别两组数据集重叠的共表达基因模块。随后,利用GEO公共数据集公布的基因表达数据(GSE24206和GSE53845)识别常见差异表达基因(DEGs)和相关功能。然后采用实验对富集到的基因进行验证。结果:通过生物信息学算法,利用WGCNA在两组数据集中鉴定出与IPF进展相关的核心基因模块。结合GSE24206和GSE53845中的基因表达数据识别出25个核心基因,其中包括补体因子H(CFH)、COL14A1、CXCL12、FNDC1、POSTN 5个关键候选基因。通过基因本体和通路分析,揭示了这些基因与IPF生物过程、分子功能和细胞组分的关联。通过蛋白质-蛋白质相互作用(PPI)网络分析,确认了CFH在IPF中的重要性。收集IPF患者的临床标本及正常标本验证,包括实时荧光定量PCR(RT-qPCR)、免疫组化和免疫印迹法进一步证实了CFH与IPF进程密切相关。结论:CFH在IPF患者中显著升高,为CFH成为治疗IPF疾病的靶点提供了依据,为IPF提供了新的治疗方式。

参考文献:

[1] RAGHU G,COLLARD H R,EGAN J J,et al.An official ATS/ERS/JRS/ALAT statement:idiopathic pulmonary fibrosis:evidence-based guidelines for diagnosis and management[J].Am J Respir Crit Care Med,2011,183(6):788-824.
[2] HUTCHINSON J,FOGARTY A,HUBBARD R,et al.Global incidence and mortality of idiopathic pulmonary fibrosis:a systematic review[J].Eur Respir J,2015,46(3):795-806.
[3] GEORGE P M,SPAGNOLO P,KREUTER M,et al.Progressive fibrosing interstitial lung disease:clinical uncertainties,consensus recommendations,and research priorities[J].Lancet Respir Med,2020,8(9):925-934.
[4] LE SAUX C J,CHAPMAN H A.Idiopathic pulmonary fibrosis:cell death and inflammation revisited[J].Am J Respir Cell Mol Biol,2018,59(2):137-138. A.病人肺组织CFH表达;B~D.分别为病人肺组织IL-1β、IL-6、TNF-α表达;E.正常肺组织CFH表达;F~H.分别为正常肺组织IL-1β、L-6、TNF-α表达 图5 病人肺组织与正常肺组织的免疫组化结果分析(比例尺100 μm,n=3) **与IPF组比较,P<0.05 图6 CFH的蛋白表达量(n=3)表4 mRNA相对表达量(x±s,n=3) 组 别mRNA相对表达量CFHIL-1βIL-6TNF-αIPF组11.775±0.7742.649±0.24816.158±0.32213.980±0.425正常组1.100±0.135a0.405±0.066b0.584±0.077a1.234±0.161a 与IPF组比较,a P<0.000 1,b P<0.01
[5] O'DWYER D N,ASHLEY S L,GURCZYNSKI S J,et al.Lung microbiota contribute to pulmonary inflammation and disease progression in pulmonary fibrosis[J].Am J Respir Crit Care Med,2019,199(9):1127-1138.
[6] LIU Y,ZHU M,GENG J,et al.Incidence and radiologic-pathological features of lung cancer in idiopathic pulmonary fibrosis[J].Clinical Respiratory J,2018,12(4):1700-1705.
[7] HUANG X,LV D,YANG X,et al.m6A RNA methylation regulators could contribute to the occurrence of chronic obstructive pulmonary disease[J].J Cellular Molecular Med,2020,24(21):12706-12715.
[8] CLARK S J,RIDGE L A,HERBERT A P,et al.Tissue-specific host recognition by complement factor H is mediated by differential activities of its glycosaminoglycan-binding regions[J].J Immunol,2013,190(5):2049-2057.
[9] GAO L,JIANG D,GENG J,et al.Hydrogen inhalation attenuated bleomycin-induced pulmonary fibrosis by inhibiting transforming growth factor-β1 and relevant oxidative stress and epithelial-to-mesenchymal transition[J].Exp Physiol,2019,104(12):1942-1951.
[10] KONG Y,FENG Z C,ZHANG Y L,et al.Identification of immune-related genes contributing to the development of glioblastoma using weighted gene co-expression network analysis[J].Front Immunol,2020,11:1281.
[11] CHOU W C,CHENG A L,BROTTO M,et al.Visual gene-network analysis reveals the cancer gene co-expression in human endometrial cancer[J].BMC Genomics,2014,15:300.
[12] YU D H,RUAN X L,HUANG J Y,et al.Analysis of the interaction network of Hub miRNAs-Hub genes,being involved in idiopathic pulmonary fibers and its emerging role in non-small cell lung cancer[J].Front Genet,2020,11:302.
[13] SIVAKUMAR P,AMMAR R,THOMPSON J R,et al.Integrated plasma proteomics and lung transcriptomics reveal novel biomarkers in idiopathic pulmonary fibrosis[J].Respir Res,2021,22(1):273.
[14] OKEMEFUNA A I,NAN R,MILLER A,et al.Complement factor H binds at two independent sites to C-reactive protein in acute phase concentrations[J].J Biol Chem,2010,285(2):1053-1065.
[15] CORTES C,DESLER C,MAZZOLI A,et al.The role of properdin and factor H in disease[J].Adv Immunol,2022,153:1-90.
[16] PILLAI-KASTOORI L,SCHUTZ-GESCHWENDER A R,HARFORD J A.A systematic approach to quantitative Western blot analysis[J].Anal Biochem,2020,593:113608.
[17] SCHAFER S C,FUNKE-CHAMBOUR M,BEREZOWSKA S.Idiopathische lungenfibrose-epidemiologie,ursachen und klinischer verlauf[J].Pathologe,2020,41(1):46-51.
[18] PATEL N M,KAWUT S M,JELIC S,et al.Pulmonary arteriole gene expression signature in idiopathic pulmonary fibrosis[J].Eur Respir J,2013,41(6):1324-1330.
[19] DEPIANTO D J,CHANDRIANI S,ABBAS A R,et al.Heterogeneous gene expression signatures correspond to distinct lung pathologies and biomarkers of disease severity in idiopathic pulmonary fibrosis[J].Thorax,2015,70(1):48-56.
[20] JIA G,CHANDRIANI S,ABBAS A R,et al.CXCL14 is a candidate biomarker for Hedgehog signalling in idiopathic pulmonary fibrosis[J].Thorax,2017,72(9):780-787.
[21] WU X.CXCL12/CXCR4:an amazing challenge and opportunity in the fight against fibrosis[J].Ageing Res Rev,2023,83:101809.
[22] 王煜州,孙票票,孙玉恒,等.中性粒细胞与肺纤维化关系的研究进展[J].东南大学学报(医学版),2023,42(1):149-153.
[23] ZHANG Y,DU W,CHEN Z,et al.Upregulation of PD-L1 by SPP1 mediates macrophage polarization and facilitates immune escape in lung adenocarcinoma[J].Exp Cell Res,2017,359(2):449-457.
[24] MORSE C,TABIB T,SEMBRAT J,et al.Proliferating SPP1/MERTK-expressing macrophages in idiopathic pulmonary fibrosis[J].Eur Respir J,2019,54(2):1802441.
[25] XING Z,GONG K,HU N,et al.The reduction of uromodulin,complement factor H,and their interaction is associated with acute kidney injury to chronic kidney disease transition in a four-time cisplatin-injected rat model[J].Int J Mol Sci,2023,24(7):6636.

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