HEPATIC REGENERATION IN VITAMIN-A-DEFICIENT RATS - CHANGES IN THE EXPRESSION OF TRANSFORMING GROWTH-FACTOR-ALPHA EPIDERMAL GROWTH-FACTOR RECEPTOR AND RETINOIC ACID RECEPTOR-ALPHA AND RECEPTOR-BETA

We have studied the effect of vitamin A deficiency on the expression o f transforming growth factor alpha (TGF-alpha), hepatocyte growth fact or, acidic fibroblast growth factor, and TCF-beta 1 after partial hepa tectomy of vitamin A-supplemented and vitamin A-deficient rats. In add ition, the expressions of epidermal growth factor receptor and retinoi c acid receptors alpha (RAR alpha) and beta (RAR beta) were studied. P artial hepatectomy was performed on the animals from the vitamin A-sup plemented and -deficient groups at the age of 10 weeks when the weight s of the animals on the deficient diet had reached a plateau, Two anim als from each group were sacrificed before the operation and also 12, 24, 48, and 72 h and 5 days after the operation. Partial hepatectomy o f the vitamin A-deficient rats leads to a focal necrosis of liver foll owed by a rapid restoration of liver mass. Expression of the TGF-alpha and epidermal growth factor receptor was highly elevated in the liver s of deficient animals after partial hepatectomy. In the vitamin A-sup plemented animals, the level of epidermal growth factor receptor was d ownregulated following partial hepatectomy. Proliferation of oval cell s in vitamin A-deficient livers following partial hepatectomy and subs equent increase in 2.1-kilobase alpha-fetoprotein mRNA was observed, s uggesting an activation of the stem cell compartment Another unexpecte d result was an inverse relationship between RAR beta and RAR alpha ex pression, the latter becoming the major species after partial hepatect omy in animals on the vitamin A-deficient regimen. The level and time course of TGF-alpha expression following partial hepatectomy was diffe rent in vitamin A-deficient animals from those supplemented with vitam in A, whereas no significant difference in the expression patterns of hepatocyte growth factor, acidic fibroblast growth factor, or TGF-beta 1 was observed between vitamin A-supplemented and -deficient animals.