{"title":"干燥综合征中参与启动cAMP信号介导的唾液分泌的胰岛素信号的关键生物标志物鉴定:NOD小鼠模型的转录组测序。","authors":"Bo Chen, Jiannan Zhou, Tianjiao Mao, Tingting Cao, Shilin Hu, Wenqi Zhang, Xueyang Li, Xiuni Qin, Xintong Liu, Nobumoto Watanabe, Jiang Li","doi":"10.1186/s12575-022-00189-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Sjogren's syndrome (SS) is an autoimmune disorder characterized by the destruction of exocrine glands, resulting in dry mouth and eyes. Currently, there is no effective treatment for SS, and the mechanisms associated with inadequate salivary secretion are poorly understood.</p><p><strong>Methods: </strong>In this study, we used NOD mice model to monitor changes in mice's salivary secretion and water consumption. Tissue morphology of the submandibular glands was examined by H&E staining, and Immunohistochemical detected the expression of AQP5 (an essential protein in salivary secretion). Global gene expression profiling was performed on submandibular gland tissue of extracted NOD mice model using RNA-seq. Subsequently, a series of bioinformatics analyses of transcriptome sequencing was performed, including differentially expressed genes (DEGs) identification, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, PPI network construction, hub gene identification, and the validity of diagnostic indicators using the dataset GSE40611. Finally, IFN-γ was used to treat the cells, the submandibular gland tissue of NOD mice model was extracted, and RT-qPCR was applied to verify the expression of hub genes.</p><p><strong>Results: </strong>We found that NOD mice model had reduced salivary secretion and increased water consumption. H&E staining suggests acinar destruction and basement membrane changes in glandular tissue. Immunohistochemistry detects a decrease in AQP5 immunostaining within acinar. In transcriptome sequencing, 42 overlapping DEGs were identified, and hub genes (REN, A2M, SNCA, KLK3, TTR, and AZGP1) were identified as initiating targets for insulin signaling. In addition, insulin signaling and cAMP signaling are potential pathways for regulating salivary secretion and constructing a regulatory relationship between target-cAMP signaling-salivary secretion.</p><p><strong>Conclusion: </strong>The new potential targets and signal axes for regulating salivary secretion provide a strategy for SS therapy in a clinical setting.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"24 1","pages":"26"},"PeriodicalIF":3.7000,"publicationDate":"2022-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9793606/pdf/","citationCount":"0","resultStr":"{\"title\":\"The Critical Biomarkers Identification of Insulin Signaling Involved in Initiating cAMP Signaling Mediated Salivary Secretion in Sjogren Syndrome: Transcriptome Sequencing in NOD Mice Model.\",\"authors\":\"Bo Chen, Jiannan Zhou, Tianjiao Mao, Tingting Cao, Shilin Hu, Wenqi Zhang, Xueyang Li, Xiuni Qin, Xintong Liu, Nobumoto Watanabe, Jiang Li\",\"doi\":\"10.1186/s12575-022-00189-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Sjogren's syndrome (SS) is an autoimmune disorder characterized by the destruction of exocrine glands, resulting in dry mouth and eyes. Currently, there is no effective treatment for SS, and the mechanisms associated with inadequate salivary secretion are poorly understood.</p><p><strong>Methods: </strong>In this study, we used NOD mice model to monitor changes in mice's salivary secretion and water consumption. Tissue morphology of the submandibular glands was examined by H&E staining, and Immunohistochemical detected the expression of AQP5 (an essential protein in salivary secretion). Global gene expression profiling was performed on submandibular gland tissue of extracted NOD mice model using RNA-seq. Subsequently, a series of bioinformatics analyses of transcriptome sequencing was performed, including differentially expressed genes (DEGs) identification, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, PPI network construction, hub gene identification, and the validity of diagnostic indicators using the dataset GSE40611. Finally, IFN-γ was used to treat the cells, the submandibular gland tissue of NOD mice model was extracted, and RT-qPCR was applied to verify the expression of hub genes.</p><p><strong>Results: </strong>We found that NOD mice model had reduced salivary secretion and increased water consumption. H&E staining suggests acinar destruction and basement membrane changes in glandular tissue. Immunohistochemistry detects a decrease in AQP5 immunostaining within acinar. In transcriptome sequencing, 42 overlapping DEGs were identified, and hub genes (REN, A2M, SNCA, KLK3, TTR, and AZGP1) were identified as initiating targets for insulin signaling. In addition, insulin signaling and cAMP signaling are potential pathways for regulating salivary secretion and constructing a regulatory relationship between target-cAMP signaling-salivary secretion.</p><p><strong>Conclusion: </strong>The new potential targets and signal axes for regulating salivary secretion provide a strategy for SS therapy in a clinical setting.</p>\",\"PeriodicalId\":8960,\"journal\":{\"name\":\"Biological Procedures Online\",\"volume\":\"24 1\",\"pages\":\"26\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2022-12-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9793606/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biological Procedures Online\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1186/s12575-022-00189-5\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biological Procedures Online","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s12575-022-00189-5","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
The Critical Biomarkers Identification of Insulin Signaling Involved in Initiating cAMP Signaling Mediated Salivary Secretion in Sjogren Syndrome: Transcriptome Sequencing in NOD Mice Model.
Background: Sjogren's syndrome (SS) is an autoimmune disorder characterized by the destruction of exocrine glands, resulting in dry mouth and eyes. Currently, there is no effective treatment for SS, and the mechanisms associated with inadequate salivary secretion are poorly understood.
Methods: In this study, we used NOD mice model to monitor changes in mice's salivary secretion and water consumption. Tissue morphology of the submandibular glands was examined by H&E staining, and Immunohistochemical detected the expression of AQP5 (an essential protein in salivary secretion). Global gene expression profiling was performed on submandibular gland tissue of extracted NOD mice model using RNA-seq. Subsequently, a series of bioinformatics analyses of transcriptome sequencing was performed, including differentially expressed genes (DEGs) identification, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, PPI network construction, hub gene identification, and the validity of diagnostic indicators using the dataset GSE40611. Finally, IFN-γ was used to treat the cells, the submandibular gland tissue of NOD mice model was extracted, and RT-qPCR was applied to verify the expression of hub genes.
Results: We found that NOD mice model had reduced salivary secretion and increased water consumption. H&E staining suggests acinar destruction and basement membrane changes in glandular tissue. Immunohistochemistry detects a decrease in AQP5 immunostaining within acinar. In transcriptome sequencing, 42 overlapping DEGs were identified, and hub genes (REN, A2M, SNCA, KLK3, TTR, and AZGP1) were identified as initiating targets for insulin signaling. In addition, insulin signaling and cAMP signaling are potential pathways for regulating salivary secretion and constructing a regulatory relationship between target-cAMP signaling-salivary secretion.
Conclusion: The new potential targets and signal axes for regulating salivary secretion provide a strategy for SS therapy in a clinical setting.
期刊介绍:
iological Procedures Online publishes articles that improve access to techniques and methods in the medical and biological sciences.
We are also interested in short but important research discoveries, such as new animal disease models.
Topics of interest include, but are not limited to:
Reports of new research techniques and applications of existing techniques
Technical analyses of research techniques and published reports
Validity analyses of research methods and approaches to judging the validity of research reports
Application of common research methods
Reviews of existing techniques
Novel/important product information
Biological Procedures Online places emphasis on multidisciplinary approaches that integrate methodologies from medicine, biology, chemistry, imaging, engineering, bioinformatics, computer science, and systems analysis.