P026. Effect of Toll-like receptor‑2 deficiency on transcriptomic profile in DSS-colitis
V. Lorén1, E. Pedrosa2, C. Sánchez1, P. Romero2, E. Cabré3, E. Domènech3, J. Lozano4, I. Cases5, J. Manyé1
1Germans Trias i Pujol, Experimental Digestive Pathology Unit, Badalona, Spain; 2Germans Trias i Pujol, Functional Genetics Unit, Badalona, Spain; 3Germans Trias i Pujol Hospital, G‑I & IBD Unit, Badalona, Spain; 4CIBERehd, Bioinformatics Unit, Barcelona, Spain; 5Insititute of Predictive and Personalized Medicine of Cancer, Badalona, Spain
Background: Toll-like receptor (TLR)‑2 plays a pivotal role in intestinal homeostasis. Given the etiopathogenic relationship between Inflammatory Bowel Disease and pattern recognition receptors polymorphisms, we characterized colonic gene expression profiles in TLR‑2 knockout (KO) and wild type (WT) mice with DSS colitis. In this study we also sought to determinate the presence of other homeostatic key issues in the bowel, perhaps masked by the strong role of TLR‑2.
Methods: We studied vehicle-treated WT (n = 3), DSS-treated WT (WTDSS, n = 5), and DSS-treated KO mice (KODSS, n = 5). Five days after starting oral DSS or vehicle treatment, mice were sacrificed. RNA from colonic samples was used for genome-wide microarray analysis (CodeLinkTM), and for corroborative qPCR. Selected genes from microarrays data analysis (false-discovery rate <0.01 and fold change >2) by LIMA‑R package were undertaken to hierarchical clustering and gene ontology by GeneCodis and GSEA software, and PubMed and MGI database.
Results: As compared to WT, WTDSS mice showed 129 and 148 up- and down-regulated genes, respectively, while only 14 and 3 genes were up- and down-regulated in KODSS. Pathway-based enrichment analysis of up-regulated genes in WTDSS identified genes related to extracellular matrix activity, while up-regulated genes in KODSS were linked to cell cycle. Down-regulated genes in both groups involved oxidative, xenobiotic and retinol metabolism.
Conclusions: (1) The DSS-induced colitis cause few changes in gene expression profile in TLR‑2 (−/−) mice, dissimilar to what happens in WT mice; (2) DSS-colitis favours extracellular-matrix-receptor interaction; (3) This does not occur in presence of TLR2 deficiency where increased cell proliferation predominates.