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Am J Physiol Regul Integr Comp Physiol 281: R1274-R1282, 2001;
0363-6119/01 $5.00
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Vol. 281, Issue 4, R1274-R1282, October 2001

Intestinal perfusion induces rapid activation of immediate-early genes in weaning rats

Lan Jiang1, Heather Lawsky2, Relicardo M. Coloso3, Mary A. Dudley3, and Ronaldo P. Ferraris3

1 Graduate School of the Biomedical Sciences, 2 New Jersey Medical School, and 3 Department of Pharmacology and Physiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103-2714

C-fos and c-jun are immediate-early genes (IEGs) that are rapidly expressed after a variety of stimuli. Products of these genes subsequently bind to DNA regulatory elements of target genes to modulate their transcription. In rat small intestine, IEG mRNA expression increases dramatically after refeeding following a 48-h fast. We used an in vivo intestinal perfusion model to test the hypothesis that metabolism of absorbed nutrients stimulates the expression of IEGs. Compared with those of unperfused intestines, IEG mRNA levels increased up to 11 times after intestinal perfusion for 0.3-4 h with Ringer solutions containing high (100 mM) fructose (HF), glucose (HG), or mannitol (HM). Abundance of mRNA returned to preperfusion levels after 8 h. Levels of c-fos and c-jun mRNA and proteins were modest and evenly distributed among enterocytes lining the villi of unperfused intestines. HF and HM perfusion markedly enhanced IEG mRNA expression along the entire villus axis. The perfusion-induced increase in IEG expression was inhibited by actinomycin-D. Luminal perfusion induces transient but dramatic increases in c-fos and c-jun expression in villus enterocytes. Induction does not require metabolizable or absorbable nutrients but may involve de novo gene transcription in cells along the villus.

metabolism; sugars; transport; villus


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