Adenovirus-transferred HNF-3 gamma conserves some liver functions in primary cultured hepatocytes of adult rats.

Hepatocyte nuclear factor-3 (HNF-3) isoforms are key factors for regulation of gene expression and differentiation in hepatocytes. HNF-3gamma is abundantly expressed in the mature liver, but down-regulated in primary cultured hepatocytes, in which some other hepatic gene expressions are also decreased. In this study, the primary hepatocytes were infected with the recombinant adenovirus carrying HNF-3gamma gene (AxCAHNF3gamma), and this led to marked induction of the HNF-3gamma gene. As a result, the expressions of albumin, catalase, and ornithine transcarbamylase (OTC) genes were also recovered to significant levels in the AxCAHNF3gamma-infected hepatocytes. Moreover, hepatocyte proliferation stimulated by epidermal growth factor (EGF) and insulin was also inhibited by AxCAHNF3gamma infection. Our results demonstrate that the enforced expression of HNF-3gamma gene can lead to conservation of some original liver functions in the primary cultured hepatocytes accompanied by morphological differentiation and growth inhibition. Copyright 1998 Academic Press.