COMPLEX REGULATION OF TGF-BETA EXPRESSION BY RETINOIC ACID IN THE VITAMIN-A-DEFICIENT RAT

We report the results of a histochemical study, using polyclonal antipeptide antibodies to the different TGF-beta isoforms, which demonstrates that retinoic acid regulates the expression of TGF-beta in the vitamin A-deficient rat. Basal expression of TGF-beta-2 diminished under conditions of vitamin A deficiency. Treatment with retinoic acid caused a rapid and transient induction of TGF-beta-2 and TGF-beta-3 in the epidermis, tracheobronchial and alveolar epithelium, and intestinal mucosa. Induction of TGF-beta-1 expression was also observed in the epidermis. In contrast to these epithelia, expression of the three TGF-beta isoforms increased in vaginal epithelium during vitamin A deficiency, and decreased following systemic administration of retinoic acid. Our results show for the first time the widespread regulation of TGF-beta expression by retinoic acid in vivo, and suggest a possible mechanism by which retinoids regulate the functions of both normal and pre-neoplastic epithelia.