EFFECTS OF CYTOKINES AND GROWTH-FACTORS ON PHOSPHORYLATED FETUIN BIOSYNTHESIS BY ADULT-RAT HEPATOCYTES IN PRIMARY CULTURE

Recently, we showed that a 59 kDa non-phosphorylated sialoprotein puri fied from rat bone matrix is the rat counterpart of bovine fetuin and human alpha(2)-HS glycoprotein and that fetuin synthesized and secrete d by adult rat hepatocytes in primary culture is mostly phosphorylated (phosphofetuin), though fetuin is known to contain no phosphorus. Her e we report that the rate of synthesis of phosphofetuin by hepatocytes in culture was reduced by inflammatory cytokines such as human interl eukin (hIL)-6, human tumor necrosis factor-alpha and hIL-1 alpha, but dose-dependently stimulated by growth factors of hepatocytes, such as hepatocyte growth factor (HGF)/scatter factor (SF), epidermal growth f actor and insulin, as determined by metabolic labeling and Northern bl ot analysis using cDNA for rat fetuin as a probe. We also showed that administration of HGF/SF stimulated gene expression of rat fetuin in v ivo. (C) 1994 Academic Press, Inc.