RETINOIC ACID INCREASES MATRIX GLA PROTEIN IN RAT PLASMA

The administration of retinoic acid to rats at dosages which achieve circulating levels of 1 muM or more causes a 40 to 50 percent increase in plasma levels of matrix Gla protein (MGP) within 24 hr. This increase is consistent with previous studies which demonstrate strong induction of MGP gene expression by 1 muM retinoic acid in several cell lines and with the presence of a putative retinoic acid responsive element in the MGP gene promoter. Retinoic acid does increase MGP levels to a far greater extent in cells than in the plasma of rats, but this could reflect partial induction of MGP by endogenous retinoic acid in the vitamin A-replete control animals. The consistent induction of MGP expression in cultured cells and in animals suggests that this small, vitamin K-dependent protein may mediate some of the known actions of retinoic acid in differentiation and development.