SIRPA在哮喘中的表达及其预警价值的研究 |
作者:徐茂竹1 2 蔡欣蕊3 秦廷洋4 莫斯维5 6 |
单位:1. 遵义市妇幼保健院, 贵州 遵义 563099; 2. 贵州省儿童医院/遵义医科大学附属医院 儿科内科, 贵州 遵义 563000; 3. 重庆医科大学, 重庆 400016; 4. 遵义医科大学 实验动物中心, 贵州 遵义 563000; 5. 遵义医科大学附属医院 医学检验科, 贵州 遵义 563000; 6. |
关键词:哮喘 SIRPA 生信分析 预警 机制 |
分类号:R562.25 |
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出版年·卷·期(页码):2025·53·第八期(1205-1210) |
摘要:
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目的:探究信号调控蛋白A(SIRPA)在哮喘中的表达及促进哮喘发生的预警价值,并探讨其调节哮喘发生的通路机制。方法:采用哮喘患者SIRPA表达及受试者工作特征(ROC)曲线分析SIRPA与哮喘发生的相关性;Western Blot和免疫荧光检测哮喘动物肺组织SIRPA基因蛋白水平;免疫组织化学分析哮喘动物肺组织中SIRPA的表达;基因集富集分析探究哮喘患者SIRPA调节哮喘发生的机制;皮尔森系数分析哮喘患者SIRPA高表达与免疫细胞富集的相关性。结果:与健康人群组相比, 哮喘患者外周血SIRPA的表达显著增加(P<0.05);哮喘患者SIRPA表达量ROC曲线下面积(AUC)=0.72,SIRPA高表达与哮喘发生呈正相关,差异有统计学意义(P<0.05);与康复人群组相比, 哮喘患者SIRPA表达显著增加(P<0.05);哮喘动物发现肺组织中SIRPA的蛋白水平显著增加(P<0.001);哮喘患者SIRPA 通过破骨细胞分化信号通路调节哮喘发生;哮喘患者SIRPA高表达与中性粒细胞的富集呈正相关,差异有统计学意义(P<0.01),与CD4 记忆T细胞呈负相关,差异有统计学意义(P<0.01)。结论:SIRPA高表达与哮喘发病相关,其发病通路可能与破骨细胞分化调控、中性粒细胞增加及CD4记忆T细胞减少有关,对哮喘诊断预警具有一定价值。 |
Objective: To explore the expression of signal-regulated protein alpha(SIRPA) in asthma and its early warning value in asthma occurrence, and to explore the pathway mechanism of its regulation of its occurrence. Methods: The correlation between SIRPA and asthma pathogenesis was analyzed by SIRPA expression and the receiver operator characteristic(ROC) curves. Western blot and immunofluorescence were used to detect the protein level of SIRPA gene in lung tissues of an asthma model. Immunohistochemistry was adopted to analyze the expression of SIRPA in asthma. Gene set enrichment analysis was employed to explore the mechanism of SIRPA in regulating asthma pathogenesis. Pearson's coefficient was used to analyze the correlation between the high expression of SIRPA and the enrichment of immune cells. Results: The expression of SIRPA in the peripheral blood of asthma patients was significantly increased compared with that of healthy subjects(P<0.05). The area under the ROC curve(AUC) of the expression of SIRPA in asthma patients was 0.72, and high expression of SIRPA was positively correlated with the development of asthma, with a statistically significant difference(P<0.05). Compared with the recovered population group, the expression of SIRPA in asthma patients was significantly increased(P<0.05). The asthma model revealed a significant increase in the protein level of SIRPA in lung tissues(P<0.001). SIRPA regulated the development of asthma through the osteoclast differentiation signaling pathway. The high expression of SIRPA in asthma was positively correlated with the enrichment of neutrophils and negatively correlated with the CD4 memory T-cells with a statistically significant difference(P<0.01). Conclusion: The high expression of SIRPA is associated with the development of asthma, and the pathway of its pathogenesis may be related to the regulation of osteoclast differentiation, the increase of neutrophils and the decrease of CD4 memory T-cells, which is valuable for the early warning of asthma diagnosis. |
参考文献:
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[1] HUANG K, YANG T, XU J, et al.Prevalence, risk factors, and management of asthma in China:a national cross-sectional study[J].Lancet, 2019, 394(10196):407-418. [2] VEILLETTE A, CHEN J.SIRPalpha-CD47 immune checkpoint blockade in anticancer therapy[J].Trends Immunol, 2018, 39(3):173-184. [3] BARCLAY A N, VAN DEN BERG T K.The interaction between signal regulatory protein alpha(SIRPalpha) and CD47:structure, function, and therapeutic target[J].Annu Rev Immunol, 2014, 32:25-50. [4] ZHOU Z, CHEN M M, LUO Y, et al.Tumor-intrinsic SIRPA promotes sensitivity to checkpoint inhibition immunotherapy in melanoma[J].Cancer Cell, 2022, 40(11):1324-1340 e1328. [5] MARTINS T A, KAYMAK D, TATARI N, et al.Enhancing anti-EGFRvIII CAR T cell therapy against glioblastoma with a paracrine SIRPgamma-derived CD47 blocker[J].Nat Commun, 2024, 15(1):9718. [6] BARCLAY A N, BROWN M H.The SIRP family of receptors and immune regulation[J].Nat Rev Immunol, 2006, 6(6):457-464. [7] AARON S D, BOULET L P, REDDEL H K, et al.Underdiagnosis and overdiagnosis of asthma[J].Am J Respir Crit Care Med, 2018, 198(8):1012-1020. [8] PAPI A, BRIGHTLING C, PEDERSEN S E, et al.Asthma[J].Lancet, 2018, 391(10122):783-800. [9] BREITENEDER H, PENG Y Q, AGACHE I, et al.Biomarkers for diagnosis and prediction of therapy responses in allergic diseases and asthma[J].Allergy, 2020, 75(12):3039-3068. [10] 张嘉芳, 张利娜, 张喜报.血清SDF-1、TIM4水平对支气管哮喘患者气道重构程度的预测价值[J].临床肺科杂志, 2024, 29(11):1681-1686. [11] LEE J W, YOON H Y, KO Y J, et al.Dual-action protein-siRNA conjugates for targeted disruption of CD47-signal regulatory protein alpha axis in cancer therapy[J].ACS Nano, 2024, 18(33):22298-22315. [12] WILLINGHAM S B, VOLKMER J P, GENTLES A J, et al.The CD47-signal regulatory protein alpha(SIRPa) interaction is a therapeutic target for human solid tumors[J].Proc Natl Acad Sci U S A, 2012, 109(17):6662-6667. [13] WANG S, WU Q, CHEN T, et al.Blocking CD47 promotes antitumour immunity through CD103(+) dendritic cell-NK cell axis in murine hepatocellular carcinoma model[J].J Hepatol, 2022, 77(2):467-478. [14] 蒋曼, 郭君妍, 杜仲, 等.靶向CD47/SIRPα信号轴免疫疗法联合治疗策略在恶性肿瘤治疗中的应用及其作用机制研究进展[J].山东医药, 2024, 64(9):104-107. [15] PAN Y F, DONG L W, WANG M, et al.Signal regulatory protein alpha negatively regulates mast-cell activation following FcepsilonRI aggregation[J].Eur J Immunol, 2013, 43(6):1598-1607. [16] SAKANO Y, SAKANO K, HURRELL B P, et al.SIRPalpha engagement regulates ILC2 effector function and alleviates airway hyperreactivity via modulating energy metabolism[J].Cell Mol Immunol, 2024, 21(10):1158-1174. [17] SUN H, DAMANIA A, MAIR M L, et al.STAT6 blockade abrogates aspergillus-induced eosinophilic chronic rhinosinusitis and asthma, a model of unified airway disease[J].Front Immunol, 2022, 13:818017. [18] SALEH H, EELES D, HODGE J M, et al.Interleukin-33, a target of parathyroid hormone and oncostatin m, increases osteoblastic matrix mineral deposition and inhibits osteoclast formation in vitro[J].Endocrinology, 2011, 152(5):1911-1922. [19] KANG J H, LIM H, LEE D S, et al.Montelukast inhibits RANKL-induced osteoclast formation and bone loss via CysLTR1 and P2Y12[J].Mol Med Rep, 2018, 18(2):2387-2398. [20] SETHI G S, GRACIAS D T, GUPTA R K, et al.Anti-CD3 inhibits circulatory and tissue-resident memory CD4 T cells that drive asthma exacerbations in mice[J].Allergy, 2023, 78(8):2168-2180. [21] BARNES P J Targeting cytokines to treat asthma and chronic obstructive pulmonary disease[J].Nat Rev Immunol, 2018, 18(7):454-466. [22] 吴雨婷, 王萌萌, 高蓉, 等.中性粒细胞相关细胞因子对哮喘的作用研究进展[J].东南大学学报(医学版), 2023, 42(6):945-950. |
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