Developmental changes of the expression of the genes regulated by retinoic acid in the small intestine of rats.

Retinoic acid (RA) serves as a hormone-like nutrient and it plays pivotal roles in cellular differentiation and proliferation in various tissues including the small intestine. In this study, we aimed to explore a possible role of RA signaling in the developing rat small intestine of perinatal (embryonic and newborn) and suckling-weaning transition period, and we investigated the changes in the expression of several genes regulated by RA. Northern blot analysis showed that both retinal dehydrogenase 1 (RALDH1) and retinal dehydrogenase 2 (RALDH2) mRNA levels were higher in 19-day fetal (2 days before birth) small intestine and then declined after birth. Retinoid X receptor alpha (RXRalpha) mRNA and retinoic acid receptor alpha (RARalpha) mRNA levels in the small intestine showed high levels in perinatal period compared with suckling-weaning transition period. RA-target genes such as retinoic acid receptor beta (RARbeta) and cellular retinol-binding protein, type II (CRBPII) mRNA levels were significantly increased in the perinatal small intestine. Furthermore, mRNA levels of hepatocyte nuclear factor-4 (HNF-4), which is one of the possible RA-target gene and a transcription factor regulating CRBPII gene expression, was also increased in the perinatal small intestine. These results suggest that the possible perinatal RA production by RALDHs might regulate various RA-target genes including CRBPII and RARalpha through RXRalpha or HNF-4 in the small intestine.