原发性干燥综合征小鼠唾液腺组织及唾液的转录组和蛋白质组分析

Analysis of transcriptome and proteome of salivary gland tissue and saliva in primary Sjogren′s syndrome mice

目的:通过对实验性干燥综合征(ESS)小鼠的唾液腺组织和唾液进行转录组学和蛋白质组学分析,探讨原发性干燥综合征(pSS)的发生机制。方法:建立ESS模型,留取唾液腺组织和唾液,分别通过高通量转录组测序和基于LC-MS/MS的蛋白质组学分析,了解唾液腺组织和唾液中相关mRNA和蛋白表达,通路富集分析用于识别异常的调控路径,并进一步进行RNA和蛋白质关联分析。结果:通过唾液腺病理检查与唾液量测定成功验证ESS模型,并鉴定出3221个差异表达基因和253个差异表达蛋白。通过对转录组学和蛋白质组学数据的整合分析,发现61个蛋白质重叠。对异常调控的基因和蛋白的富集通路分析显示,与肾素-血管紧张素系统(RAS)、溶酶体和细胞凋亡的信号通路显著相关,其中AGT、Fn1、Klk1b26、Klk1、Klk1b5、Klk1b3在转录和蛋白水平上具有一致的调控趋势,可能是pSS的潜在诊断生物标志物。结论:pSS致病机制可能与RAS、溶酶体和细胞凋亡信号通路相关,AGT、Fn1、K1ks可能是pSS发病过程的关键分子。

Objective:To analyze the transcriptome and proteome of salivary gland tissue and saliva in experimental Sj ogren′s syndrome(ESS)mice for further exploring the pathogenesis of primary Sjogren′s syndrome(pSS).Methods:The ESS mice model was established,the salivary gland tissue and saliva were harvested,and the relevant mRNA and protein expressions in salivary gland tissue and saliva were detected using high-throughput transcriptome sequencing and proteomic analysis based on LC-MS/MS,respectively.The pathway enrichment analysis was used to identify the abnormal regulatory pathways,and the further association analysis of RNA and protein was conducted.Results:The ESS model was successfully verified by pathological examination of salivary glands and saliva volume measurement,and 3221 differentially expressed genes and 253 differentially expressed proteins were identified.The results of integrated analysis of transcriptomic and proteomic data showed that 61 proteins overlapped.The results of the enrichment pathways of abnormally regulated genes and proteins analysis showed that the renin-angiotensin system(RAS)and lysosome were significantly related to the apoptosis signaling pathways.The transcription and protein levels of AGT,Fn1,Klk1b26,Klk1,Klk1b5 and Klk1b3 were consistent regulatory trends,which might be a potential diagnostic biomarker of pSS.Conclusions:The pathogenesis of pSS may be related to the RAS,lysosome and apoptosis signaling pathway,and the AGT,Fn1 and K1ks may be the key molecules of the pathogenesis of pSS.