摘要
目的探讨胸腺增龄性萎缩与胸腺上皮细胞(thymus epithelial cells,TECs)内参与胸腺发育KGF、Foxp3、Foxn1和IL-6等基因表达的相关性。方法将18只无特定病原体(specific pathogen free,SPF)小鼠按月龄分组,每组6只。无菌取胸腺,应用实时定量聚合酶链式反应(real-time quantitative PCR,RT-PCR)检测TECs细胞中KGF、Foxp3、Foxn1和IL-6等基因的表达。结果小鼠TECs细胞中KGF、Foxp3、Foxn1和IL-6基因表达在随着年龄增加而变化,3、10、16月龄的小鼠KGF表达量分别为(0.90±0.06),(0.58±0.07)和(0.18±0.07),差异具有统计学意义(P值分别为0.030,0.020,<0.001);Foxp3表达量分别为(0.93±0.10),(0.60±0.08)和(0.20±0.06),差异具有统计学意义(P值分别为0.020,0.020,<0.001);Foxn1表达量分别为(0.92±0.09),(0.63±0.09)和(0.16±0.08),差异具有统计学意义(P值分别为0.020,0.010,<0.001);IL-6表达量分别为(0.33±0.11),(0.46±0.06),(0.88±0.09),差异具有统计学意义(P值分别为0.052,0.001,<0.001)。同时,胸腺质量的增龄性减少与TECs细胞KGF、Foxp3、Foxn1和IL-6等表达相关性结果显示,小鼠TECs细胞KGF、Foxp3和Foxn1在mRNA水平表达与胸腺增龄性萎缩(胸腺质量)情况呈正相关(KGF:r=0.941,R^(2)=0.886,P<0.001。Foxp3:r=0.939,R^(2)=0.881,P<0.001。Foxn1:r=0.918,R^(2)=0.842,P<0.001),而IL-6的mRNA表达与胸腺增龄性萎缩(胸腺质量)情况呈负相关(r=-0.866,R^(2)=0.749,P<0.001)。结论胸腺基质微环境增龄性变化和胸腺发育关键基因表达增龄性改变是导致小鼠胸腺增龄性萎缩的主要原因,提示KGF、Foxp3和Foxn1等基因的时序性表达调节胸腺增龄性萎缩的进程。
Objective To investigate the relationship between age-related thymus involution and mRNA expression of thymic KGF,Foxp3,Foxn1,IL-6 genes gene in thymus epithelial cells(TECs).Methods Specific pathogen free(SPF)mice were grouped according to the age,with 6 mice in each group.Thymus was removed aseptically,and the expression of KGF,Foxp3,Foxn1,and IL-6 in TECs was detected byreal-time quantitative PCR(RT-PCR).Results The expression of KGF,Foxp3,Foxn1 and IL-6 genes in mouse TECs cells changed with age.The levels of KGF in mice aged 3,10 and 16 months were(0.90±0.06),(0.58±0.07)and(0.18±0.07),and the difference was statistically significant(P value was 0.030,0.020,<0.001).Foxp3 expression levels were(0.93±0.10),(0.60±0.08)and(0.20±0.06),respectively,and the differences were statistically significant(P values were 0.020,0.020,<0.001).Foxn1 expression levels were(0.92±0.09),(0.63±0.09)and(0.16±0.08),and the differences were statistically significant(P values were 0.020,0.010,<0.001).Il-6 expression levels were(0.33±0.11),(0.46±0.06)and(0.88±0.09),with statistically significant differences(P values were 0.052,0.001,<0.001).Meanwhile,the correlation between the age-related reduction in thymus mass and the expression of KGF,Foxp3,Foxn1 and IL-6 in TEC cells showed that the levels of expression of KGF,Foxp3 and Foxn1 at the mRNA in mouse TECS were positively correlated with the age-related atrophy of the thymus(thymus mass)(KGF:r=0.941,R^(2)=0.886,P<0.001).(Foxp3:r=0.939,R^(2)=0.881,P<0.001.Foxn1:r=0.918,R^(2)=0.842,P<0.001).And IL-6 mRNA expression was negatively correlated with thymic ageing atrophy(thymic mass)status(r=-0.866,R^(2)=0.749,P<0.001).Conclusion Age-related changes in the thymic stromal microenvironment and age-related alterations in the expression of key thymic development genes are the main causes of age-related atrophy of the thymus in mice,suggesting that KGF Temporal expression of genes such as Foxp3 and Foxn1 regulates the progression of age-related thymus involution.
作者
王长山
杨飞宇
李丽
Wang Changshan;Yang Feiyu;Li Li(Institute of Translational Medicine,University of Chinese Academy of Sciences Shenzhen Hospital(Guangming),Shenzhen 518106,China;Department of Pediatrics,University of Chinese Academy of Sciences Shenzhen Hospital(Guangming),Shenzhen 518106,China)
出处
《国际免疫学杂志》
CAS
2022年第4期349-356,共8页
International Journal of Immunology
基金
广东省医学科学技术研究基金(A2020588)
深圳市科技计划-基础研究专项(自然科学基金)(JCYJ20210324141008021)
深圳市光明区经济发展专项资金卫生系统博士创新科研项目(2020R01079、2020R01075)
深圳市光明区经济发展专项资金科创局软科学研究项目(2021R01129、2021R01056)
中国科学院大学深圳医院重点科研项目(HRF-2020003,HRF-2020007)。
关键词
胸腺上皮细胞
KGF
FOXP3
Foxn1
IL-6
胸腺增龄性萎缩
Thymus epithelial cells
Keratinocyte growth factor
Forkhead box P3
Forkhead box N1
IL-6
Age-related thymus involution
