HEPATOCYTE GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-BETA REGULATE6-PHOSPHOFRUCTO-2-KINASE FRUCTOSE-2,6-BIPHOSPHATASE GENE-EXPRESSION IN RAT HEPATOCYTE PRIMARY CULTURES/
M. Joaquin et al., HEPATOCYTE GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-BETA REGULATE6-PHOSPHOFRUCTO-2-KINASE FRUCTOSE-2,6-BIPHOSPHATASE GENE-EXPRESSION IN RAT HEPATOCYTE PRIMARY CULTURES/, Biochemical journal, 314, 1996, pp. 235-240
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.