Complex regulation of TGFβ 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 TGFβ isoforms, which demonstrates that retinoic acid regulates the expression of TGFβ in the vitamin A-deficient rat. Basal expression of TGFβ2 diminished under conditions of vitamin A deficiency. Treatment with retinoic acid caused a rapid and transient induction of TGFβ2 and TGFβ3 in the epidermis, tracheobronchial and alveolar epithelium, and intestinal mucosa. Induction of TGFβ1 expression was also observed in the epidermis. In contrast to these epithelia, expression of the three TGFβ 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 TGFβ expression by retinoic acid in vivo, and suggest a possible mechanism by which retinoids regulate the functions of both normal and pre-neoplastic epithelia.