Physiological Genomics and the Gastrointestinal Tract
Sponsored by the APS Physiological Genomics Group

The gastrointestinal tract consists of heterogenous, relatively large and semiautonomous organs whose integrated functions allow the digestion, secretion and/or absorption of a vast array of nutrients and electrolytes. Over the past several years researchers have gained enormous insights into epithelial cell function in physiological and pathophysiological processes occurring in those organs.   In this symposium, we present an integrative approach that describes the use of high throughput genomic tools and accompanying analytical methods to characterize the role of several epithelial genes in health and disease.  In the stomach, gastrin-deficient mice have a severe impairment in acid secretion.  The first speaker will describe recent results of analysis of gastrin-regulated gene expression in purified parietal cells and mixed cell populations from the stomach of gastrin-deficient and wild-type mice.   Gene expression profiling by Affymetrics microarray analysis demonstrated key changes in gastrin target cells: parietal cells and enterochromaffin like (ECL) cells. The results will be presented in context of the physiologic impairment in acid secretion.  To understand the mechanisms involved in the development of acute pancreatitis, the second speaker will describe gene profiling studies comparing gene expression in control rats and in three models of acute pancreatitis.  The results show a common induction of genes with opposing functions including pro- and anti- inflammatory, pro- and anti- coagulation, as well as pro- and anti-apoptotic.   The results also implicate endoplasmic reticular stress mechanisms as major components regulating gene expression in the injured pancreatic acinar cell.  The third speaker will summarize results on genetic and genomic studies in celiac disease.  Gene expression and laser capture microdissection studies point to impaired integrity of the intestinal barrier and tight junctions as an underlying mechanism.  However, impaired integrity of this barrier could represent a broader phenomena contributing to autoimmune disorders other than celiac disease.   The final speaker will review the lifespan of the cells along the crypt-villus in the small intestine and how differences in cell maturity influence the response to regulatory signals influencing nutrient absorption.  The molecular signals currently thought to regulate differentiation of the absorptive enterocyte (e.g. matrix-enterocyte communication through integrins as well as the role of the transcription factors cdx-2, HNF-1 and GATA  4-6) will also be described.  Finally, available microarray, ChIP, and bioinformatics data relevant to the molecular regulation of enterocyte differentiation will be presented.