HEPATOCYTE GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-BETA REGULATE6-PHOSPHOFRUCTO-2-KINASE FRUCTOSE-2,6-BIPHOSPHATASE GENE-EXPRESSION IN RAT HEPATOCYTE PRIMARY CULTURES/

Hepatocyte growth factor (HGF) and transforming growth factor beta (TG F-beta) are believed to be of major importance for hepatic regeneratio n after liver damage. We have studied the effect of these growth facto rs on fructose 2,6-bisphosphate (Fru-2,6-P-2) levels and the expressio n of phosphofructo-2-kinase/fructose-2,6-bisphosphatase (6PF2K/Fru-2,6 -BPase) in rat hepatocyte primary cultures. Our results demonstrate th at HGF activates the expression of the 6PF2K/Fru-2,6-BPase gene by inc reasing the levels of its mRNA. As a consequence of this activation, t he amount of 6PF2K/Fru-2,6-BPase protein and 6-phosphofructo-2-kinase activity increased, which was reflected by a rise in Fru-2,6-P-2 level s. In contrast, TGF-beta decreased the levels of 6PF2K/Fru-2,6-BPase m RNA, which led to a decrease in the amount of 6PF2K/Fru-2,6-BPase prot ein and Fru-2,6-P-2. The different actions of HGF and TGF-beta on 6PF2 K/Fru-2,6-BPase gene expression are concomitant with their effect on c ell proliferation. Here we show that, in the absence of hormones, prim ary cultures of hepatocytes express the F-type isoenzyme. In addition, HGF increases the expression of this isoenzyme, and dexamethasone act ivates the L-type isoform. HGF and TGF-beta were able to inhibit this activation.