Retinoic acid (RA) is produced via two sequential reactions of retinol dehydrogenases (RDHs) and retinal dehydrogenases (RALDHs). We found that primary cultured mouse hepatocytes on a single collagen gel gradually lost hepatocyte specific morphology, and that another collagen gel overlay remarkably recovered it. The levels of albumin and liver-dominant expressed RDHs expression in hepatocytes paralleled their morphological change, decreased during single collagen gel culture, and were up-regulated by sequential collagen overlay. Quite similar to the expression changes, albumin and those RDHs' mRNA expression levels increased along with liver differentiation during pre- and postnatal liver development. Our data supports that all-trans and 9-cis RA, catalyzed by the RDHs, indeed play an important role in liver differentiation and regeneration.
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