Mo2037 Phosphodiesterase 2A Mediate Neonatal Inflammation-Induced Visceral Hypersensitivity in a Mouse Model of Irritable Bowel Syndrome

Abstract

G A A b st ra ct s in each disease type. Figure 1 shows the number of differentially regulated transcripts in various comparisons. IBS vs CD showed the highest number of deregulated transcripts (N= 686). Table 1 shows GO terms, associated genes and p values inferred from functional annotation clustering for all the comparisons. Clustering revealed upregulation of inflammatory genes (e.g., CD38molecule; TRGC2: T-cell receptor gamma locus; IGHG4: Immunoglobulin heavy constant gamma 4 (G4M marker) for both CD and UC compared to IBS. There were 4 transcripts deregulated between IBS and HCs. microRNA miR-4461 was significantly downregulated (FC: -2.2, p=0.006) in IBS compared to HCs. However, at a lower fold change cutoff (FC>1.3), inflammation and defense response associated genes, such as NFKB1A, S100 Calcium Binding Protein A12 (S100A12), NCF1B, were upregulated in IBS patients vs. HCs. miR-27A, reported as a class of adipogenic inhibitors, was upregulated in IBS patients. Most genes that had significantly different expressions in IBS vs. HCs were unannotated. Conclusions:Our findings suggest that while inflammatory genes were modestly upregulated in IBS vs. HCs, they were much lower compared to IBD. Interestingly, miR-27, which is upregulated in obesity, is also upregulated in IBS, suggesting that there may be a shared pathophysiologic mechanism. Thus, comparing mRNA profiles of IBS to that of GI disease controls such as IBD and healthy controls may lead to a better understanding of the pathophysiology of IBS and potentially a diagnostic biomarker. Gene Ontology (GO) Terms Associated with IBS vs Healthy and Disease Controls