Nitric oxide pathway-related gene alterations in inflammatory bowel disease
2012 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, Vol. 47, no 11, 1283-1297 p.Article in journal (Refereed) Published
Objective: To reveal specific gene activation in nitric oxide (NO)-related inflammation we studied differential gene expression in inflammatory bowel disease (IBD). Methods. Total RNA was isolated from 20 biopsies of inflamed mucosa from Crohn's disease (CD) and ulcerative colitis (UC) patients each as well as from six controls, labeled with 32P-dCTP and hybridized to a human NO gene array. Significant genes were analyzed for functional gene interactions and heatmaps generated by hierarchical clustering. A selection of differentially expressed genes was further evaluated with immunohistochemical staining. Results. Significant gene expression differences were found for 19 genes in CD and 23 genes in UC compared to controls, both diseases with high expression of ICAM1 and IL-8. Correlation between microarray expression and corresponding protein expression was significant (r 0.47, p 0.002). Clustering analysis together with functional gene interaction analysis revealed clusters of coregulation and coexpression in CD and UC: transcripts involved in angiogenesis, inflammatory response mediated by the transcription factor hypoxia-inducible factor 1, and tissue fibrosis. Also, a fourth cluster with transcripts regulated by the transcription factor Sp1 was found in UC. Conclusions. Expression analysis in CD and UC revealed disease-specific regulation of NO-related genes, which might be involved in perpetuating inflammatory disease activity in IBD.
Place, publisher, year, edition, pages
2012. Vol. 47, no 11, 1283-1297 p.
Cluster analysis, Crohn's disease, Gene expression profiling, Microarray analysis, Ulcerative colitis, deoxycytidine triphosphate, hypoxia inducible factor 1, interleukin 8, nitric oxide, phosphorus 32, transcription factor Sp1, adult, aged, angiogenesis, article, clinical article, colon biopsy, controlled study, correlation analysis, Crohn disease, disease activity, female, gene, gene activation, gene control, gene expression, gene interaction, genetic analysis, genetic association, genetic transcription, human, human tissue, ICAM1 gene, immunohistochemistry, isotope labeling, male, mucosa inflammation, nucleotide sequence, priority journal, protein expression, RNA isolation, statistical significance
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-184935DOI: 10.3109/00365521.2012.706830ISI: 000309938200004OAI: oai:DiVA.org:uu-184935DiVA: diva2:570476