中国实验动物学报2024，Vol.32Issue(3)：297-306,10.DOI:10.3969/j.issn.1005-4847.2024.03.003
母体炎性暴露对子代小鼠受IRBP抗原诱导的葡萄膜炎的影响
Impact of embryonic uveitis exposure on response of mouse offspring to interphotoreceptor retinoid-binding protein-induced experimental autoimmune uveitis
摘要
Abstract
Objective To investigate the effect of embryonic inflammatory exposure on the response of mouse offspring to interphotoreceptor retinoid-binding protein(IRBP)-induced experimental autoimmune uveitis(EAU).Methods RNA transcriptome sequencing data from eyeballs of C57BL/6J mouse offspring born to mothers with active EAU were used to screen immune-associated differentially expressed genes in the eyes of the exposed offspring.Gene fragments overlapping in the two datasets were screened using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses to identify biological pathways associated with the gene fragments.Hub genes were identified from these intersecting genes by protein-protein interaction network analysis.EAU models of maternal uveitis were established by immunization with IRBP651-670,and expression levels of the pivotal genes in the offspring exposed to inflammation by maternal uveitis were examined by fluorescence quantitative polymerase chain reaction.EAU severity,T lymphocyte proliferation,and serum cytokines were detected to investigate the immune effect in offspring from mothers with an active inflammation response to IRBP induction.Results Microarray analysis identified 72 immune-related differentially expressed genes in exposed samples compared with the findings in control samples.These genes were mainly enriched in Toll-like receptor signaling,mitogen-activated protein kinase signaling,and B cell receptor signaling pathways.Protein-protein interaction network interaction analysis screened out four hub genes,Psmc5,Psmc3,Psmd4,and Psmd8,and mRNA levels of these four genes were increased in the adult offspring from mothers with active uveitis compared with the findings in healthy offspring.In addition,the group induced with 150 μg IRBP showed an increase in the severity of clinical and pathological outcomes in offspring with EAU affected by active inflammation,compared with the healthy offspring group(P=0.0087,P=0.0410).Meanwhile,T cell proliferation in the offspring was enhanced during the inflammatory activity stage and secretion of the inflammatory cytokines interleukin(IL)-17 and IL-6 was increased(P=0.0450,P=0.0300).Conclusions Psmc5,Psmc3,Psmd4,and Psmd8 may be important genes exacerbating uveitis in offspring of mothers with active uveitis,associated with increased T cell proliferation and production of IL-17 and IL-6.关键词
实验性自身免疫性葡萄膜炎/胚胎炎性暴露/子代/枢纽基因/炎症严重程度Key words
experimental autoimmune uveitis/embryonic inflammatory exposure/offspring/pivotal gene/inflammation severity分类
生物科学引用本文复制引用
徐菲,刘健萍,董世访,皇辉,龚心怡,胡开娇,陈飞兰..母体炎性暴露对子代小鼠受IRBP抗原诱导的葡萄膜炎的影响[J].中国实验动物学报,2024,32(3):297-306,10.基金项目
国家自然科学基金(81670843),重庆医科大学未来医学青年创新团队发展支持计划(W0164). Funded by the National Natural Science Foundation Project(81670843),Chongqing Medical University Program for Youth Innovation in Future Medicine(W0164). （81670843）
