环化鸟苷酸—腺苷酸合成酶—干扰素基因刺激因子信号通路在干燥综合征唇腺组织中的表达研究  

Expression of cGAS-STING signaling pathway molecules in labial gland tissue of Sjögren′s syndrome

作　　者：李霞[1] 田真[1] 万东山 赵义[1] Li Xia;Tian Zhen;Wan Dongshan;Zhao Yi(Department of Rheumatology&Allergy,Xuanwu Hospital,Capital Medical University,Beijing 100053,China;Department of Neurology,Xuanwu Hospital,Capital Medical University,Beijing 100053,China)

机构地区：[1]首都医科大学宣武医院风湿免疫-变态反应科,北京100053 [2]首都医科大学宣武医院神经内科,北京100053

出　　处：《中华风湿病学杂志》2024年第10期723-727,I0004,共6页Chinese Journal of Rheumatology

基　　金：首都医科大学宣武医院国家自然科学基金青年培育项目(QNPY2021025)。

摘　　要：目的初步探讨环化鸟苷酸—腺苷酸合成酶(cGAS)—干扰素基因刺激因子(STING)信号通路在原发性干燥综合征(pSS)患者唇腺组织中的表达情况及与疾病特征间的相关性。方法收集2021年1月至12月首都医科大学宣武医院就诊的19例确诊pSS及性别年龄匹配的7例单纯口干症对照组的临床资料及唇腺标本,进行cGAS免疫荧光染色,蛋白印迹法进一步测定及确证cGAS-STING信号通路分子[cGAS、磷酸化STING(pSTING)、磷酸化干扰素调节因子3(pIRF3)及磷酸化TBK结合激酶1(pTBK1)]在2组唇腺组织中的表达水平。正态分布资料组间比较采用t检验,非正态分布资料组间比较用Mann-WhitneyU检验。并采用Spearman相关分析探究临床特征与分子表达水平之间的相关性。以P<0.05为差异有统计学意义。结果免疫荧光法显示pSS组唇腺组织腺泡间质内可见表达cGAS阳性的细胞大量浸润,而在对照组唇腺组织内不表达或少量表达cGAS阳性细胞,2组差异具有统计学意义(t=3.87,P=0.001)。同时pSS患者唇腺组织cGAS表达水平与灶性指数(FS)具有相关性(r=0.55,P=0.014)。进一步行蛋白印迹分析,pSS组与对照组唇腺组织表达cGAS与pSTING差异有统计学意义(0.73±0.39与0.18±0.05,t=2.38,P=0.049和0.91±0.17与0.23±0.10,t=2.17,P=0.043)。并且Spearman相关性分析发现,唇腺组织中cGAS的表达水平与pSTING的表达具有相关性(r=0.82,P=0.001)。而唇腺组织中cGAS的表达水平与临床表现、血清学指标(IgG水平、RF滴度、C3水平和自身抗体阳性率)及病情活动度(ESSDAI评分)无相关性。结论cGAS-STING信号通路在pSS患者唇腺组织中存在激活,可能参与了其发病过程。ObjectiveTo investigate the expression of cGAS-STING signaling pathway molecules in labial gland specimen of primary Sjögren′s syndrome(pSS)patients and its correlation with disease characteristics.MethodsClinical data and labial gland specimens were collected from 19 patients diagnosed with pSS who visited Xuanwu Hospital,Capital Medical University,from January 2021 to December 2021,along with a control group of 7 gender-and age-matched individuals with isolated xerostomia.We performed immunofluorescence staining for cGAS on labial gland specimens,and Western blot analysis was further utilized to confirm the expression levels of cGAS-STING signaling pathway-related molecules(cGAS,pSTING,pIRF3 and pTBK1)in the labial gland tissues of both groups.For normally distributed data,t test was employed for comparison between groups,while the Mann-Whitney U test was used for non-normally distributed data.And Spearman's correlation analysis was utilized to explore the correlation between clinical characteristics and molecular expression levels.P value<0.05 was considered statistically significant.ResultsImmun-ofluorescence analysis showed significant infiltration of cGAS-positive cells in the labial gland tissues of the pSS group,while the control group exhibited no or minimal expression of cGAS-positive cells and there was a statistical difference between the two groups(t=3.87,P=0.001).Moreover,the expression level of cGAS in labial gland tissues of pSS patients had a positive correlation with the focus scores(r=0.55,P=0.014).Western blot analysis revealed statistically significant differences in the expression of cGAS and pSTING between the pSS group and the control group in labial gland tissues(0.73±0.39 vs.0.18±0.05,t=2.38,P=0.049 and 0.91±0.17 vs.0.23±0.10,t=2.17,P=0.043).Additionally,a correlation between the expression levels of cGAS and pSTING in labial gland tissues was found according to Spearman correlation analysis(r=0.823,P=0.001).However,there was no correlation between the expression level of cGAS in

关 键 词：干燥综合征 cGAS-STING信号通路 分子表达 Ⅰ型干扰素 

分 类 号：R593.2[医药卫生—内科学]