ANALYSIS OF CLONED CDNAS DIFFERENTIALLY EXPRESSED IN ADAPTING REMNANTSMALL-INTESTINE AFTER PARTIAL RESECTION

After partial resection, the remnant small intestine undergoes an adap tive response. Little is known about the molecular and cellular basis of intestinal adaptation. To identify genes transcriptionally regulate d in response to loss of functional bowel surface area, we have isolat ed cDNAs differentially expressed in the adaptive ileum 48 h after 70% proximal small intestinal resection. A cDNA library constructed from the remnant ileum of rats subjected to resection was screened using su btractive hybridization techniques. Several groups of cDNA clones that were induced during intestinal adaptation were isolated. The first in cluded liver fatty acid binding protein, apolipoprotein A-TV, cellular retinol binding protein II, and ileal lipid binding protein. These al l encode proteins involved in the absorption, metabolism, and traffick ing of nutrients. A second group included the catalytic subunit of pro tein phosphatase 1 delta, a 78-kDa glucose-regulated protein (grp78; a glucose-regulated member of the 70-kDa he at-shock protein family), a nd several pancreatitis-associated proteins. A third group of induced genes contained novel cDNAs. To better characterize the adaptive respo nse, the temporal, spatial, and cellular patterns of expression of sev eral of these genes were analyzed with the use of immuno-histochemical and in situ hybridization techniques. These studies indicate that dur ing early adaptation, genes involved in nutrient trafficking, protein processing, and cell cycle regulation are transcriptionally regulated in the residual small intestine in distinct temporal and regional patt erns consistent with a complex multifaceted response to intestinal res ection.