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1. Biomarkers And Potential Therapeutic Targets Of Systemic Sclerosis With Interstitial Lung Disease 2. Analysis Of Plasma Exosomal MiRNA And Protein Expression In Takayasu Arteritis

Posted on:2022-04-27Degree:MasterType:Thesis
Country:ChinaCandidate:B Q HuangFull Text:PDF
GTID:2514306350498154Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective:This study aims to analyze gene expression in lung tissue of patients with systemic sclerosis associated interstitial lung disease(SSc-ILD)to identify biomarkers and potential therapeutic targets and to examine its possible role in the pathogenesis of SSc-ILD.Methods:We obtained datasets from Gene Expression Omnibus(GEO)database,and calculated the co-expressed differentially-expressed-genes(DEGs)in two chips,then analyzed the function,signaling pathways and the protein-protein interaction network of the DEGs.Besides,we verified the DEGs related to SScILD by four databases of Comparative Toxicogenomics Database(CTD),GENE,GeneCards and DisGeNET,respectively.And we analyzed the SSc-ILD-gene-drug network by CTD database.Finally,we analyzed the expression of genes related to SSc-ILD in different organs,tissues and cells of the human body by the HPA database.Results:There were 230 co-expressed DEGs in the two chips,of which 59 genes were up-regulated and 171 genes were down-regulated.There were 27 genes related to SSc-ILD in CTD,GENE,DisGeNET and GeneCards databases.Combined with the analysis results of two chips and 4 databases,IL6,CXCL8,CCL2,and ICAM1 might be potential biomarkers and potential therapeutic targets of SSc-ILD.These 4 genes were related to cyclophosphamide,azathioprine,and glucocorticoids that are currently used to treat SSc-ILD.Conclusion:IL6,CXCL8,CCL2 and ICAM1 were the key genes of SSc-ILD,which might be involved in the pathogenesis of SSc-ILD by regulating the process of inflammation and fibrosis,and were expected to be biomarkers and potential therapeutic targets of SSc-ILD.Objective:Detected the miRNA and protein carried by exosomes in the plasma of patients with newly diagnosed Takayasus arteritis(TAK),and analyzed their possible role in the pathogenesis of TAK.Methods:We collected 10 age-and gender-matched newly diagnosed TAK patients and 5 healthy controls,used RNA-Seq and protein mass spectrometry to detect miRNAs and proteins carried by exosomes in the plasma,screened out differentially expressed miRNAs and proteins(DE-miRs and DEPs),and performed hierarchical cluster analysis,function and signal pathway enrichment analysis of DE-miRs and DEPs.Finally,we screened out miRNAs and proteins related to TAK,and explored its possible role in the pathogenesis of TAK.Results:Compared with the healthy control,there were 29 DE-miRs carried by exosomes in the plasma of newly diagnosed patients with TAK,of which 17 were up-regulated and 12 were down-regulated;and there were 357 DEPs,of which 236 were up-regulated,121 were down-regulated.MiR-21-5p?miR-200c-3p?miR34a-5p?miR-22-3p?miR-143-3p?DSP?KNG1?KLKB1 were related to TAK,which might be involved in the pathogenesis of TAK,and were expected to be biomarkers of TAK.Conclusion:MiR-21-5p?miR-200c-3p?miR-34a-5p?miR-22-3p?miR-143-3p?DSP?KNG1?KLKB1 carried by exosomes in the plasma might participate in the pathogenesis of TAK by regulating vascular function,vascular remodeling and other processes,and were supposed to be biomarkers and therapeutic targets of TAK.
Keywords/Search Tags:systemic sclerosis, interstitial lung disease, differentially expressed gene, biomarkers, therapeutic targets, Takayasus arteritis, exosomes, microRNA, protein, pathogenesis, biomarker
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