Temporal pattern of rat small intestinal gene expression with refeeding.
Studies were carried out to elucidate the molecular mechanisms underlying small intestinal epithelial growth. Adult rats were fasted for 4 days and then refed a chow diet for up to 48 h. Histological examination confirmed the sequential occurrence of mucosal atrophy and hyperplasia. Northern blot analyses of RNA derived from small intestinal mucosal scrapings revealed a striking pattern of alterations in the expression of two different categories of genes. There were very early increases in the expression of c-fos and c-jun, reflecting the mitogenic response to refeeding that occurs within the crypt compartment. Studies using the protein synthesis inhibitor cycloheximide suggest that c-fos and c-jun are part of the "immediate-early" response of the small intestine. At later time points after the refeeding stimulus, differential changes occurred in the expression of the brush-border enzymes, lactase, and intestinal alkaline phosphatase (IAP). Refeeding caused a decrease in lactase gene expression and an increase in the expression of the 3.0-kb IAP mRNA species, reflecting a return of the villus phenotype to the normal fed state. Thus we have demonstrated a complex and temporally related pattern of gene expression within the small intestinal epithelium upon refeeding. The results provide insight into the relationship between the processes of intestinal growth and differentiation.
Hodin
R A
RA
Department of Surgery, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02215.
Graham
J R
JR
Meng
S
S
Upton
M P
MP
D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D004798:Enzymes / Q000235:genetics; D005215:Fasting; D005502:Food; D015870:Gene Expression / Q000187:drug effects; D007421:Intestine, Small / Q000502:physiology*; D008297:Male; D008871:Microvilli / Q000201:enzymology; D011519:Proto-Oncogenes; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D004798:Enzymes; D003513:Cycloheximide