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 (RXRα) mRNA and retinoic acid receptor alpha (RARα) 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 (RARβ) 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 RARα through RXRα or HNF-4 in the small intestine.