Mo1816 The NHE3 Interacting PDZ Protein NHERF2 is Strongly Lipid Raft-Associated and Determines the Raft Association of the Apical Na+/H+ Exchanger NHE3 in Murine Small Intestinal Brush Border Membrane

Background and Aim. MicroRNAs (miRNAs) have been shown to play important roles in various biological processes including cell proliferation and the immune response, and are also involved in intestinal epithelial cell differentiation. Many studies have examined global miRNA expression in health and disease. However, the effect of synthesis of a specific protein in a particular tissue on miRNA expression in the same tissue has not yet been explored. In the present study we investigated the effect of colonic PepT1 expression on miRNA synthesis in the colon of control mice and in mice experiencing inflammation. Methods Six weeks old villin-hPepT1+/+ Tg mice and FVB/N male mice were used for this study. Colitis was induced by the addition of 3 % (w/v) dextran sodium sulfate to the drinking water with appropriate controls. RNA was extracted from the colon tissue was processed further for microarray analysis. MiRNA's that are differentially expressed in DSS treated mice with that of control were checked by RT-PCR. MiRNA protein targets prediction were obtained from PicTar, MicroCosm and TargetScan. Common gene targets were identified by Matchminer program. The functional annotation of each protein was analyzed through clusters formed by DAVID. Results We have shown here that colonic PepT1 expression specifically deregulates colonic miRNA synthesis both in mice experiencing induced colitis and controls. Colonic PepT1 expression-dependent deregulation of colonic miRNA synthesis potentially affects the expression levels of many proteins. Such changes do not seem to modulate the mouse phenotype in a non-inflammatory environment but may play an important role in aggravation of induced colitis. Conclusion This is the first report to show that expression of a specific protein in a particular tissue may affect miRNA synthesis in the same tissue. In addition, it may be that colonic miRNA expression regulated by colonic PepT1 plays an important role during induced colitis.