Production and activation of hepatocyte growth factor in acute renal failure

Hepatocyte growth factor (HGF) facilitates the regeneration of injured kidn ey in acute renal failure (ARF). HGF is produced as a single-chain precurso r by cells of mesenchymal origin and is converted to a biologically active, heterodimeric molecule by proteolytic processing. We studied HGF mRNA and protein levels in systemic organs of glycerol-induc ed ARF rats, a model of crush syndrome. HGF protein concentration of tissue homogenate was measured by ELISA. Both mRNA and protein levels were increa sed in liver and spleen at 24 hours after the glycerol injection whereas HG F protein level was decreased in the injured kidney. Expression of HGF rece ptor/c-met mRNA was elevated only in the kidney. These results suggest that HGF supplied in an endocrine manner may play an important role in the rege nerating process following ARF. Next, we measured serum HGF concentration by ELISA in 8 ARF patients caused by crush syndrome and the molecular size of serum HGF was determined by im munoblotting. Although serum HGF levels elevated in all patients', the HGF levels did not associate with their prognoses. While a single-chain molecul e was predominantly observed in sera from chronic renal failure patients an d healthy subjects, the majority of serum HGF was a heterodimeric form in 7 ARF patients. In one patient who developed disseminated intravascular coag ulation syndrome and had a poor prognosis, a single-chain molecule was pred ominant although the serum HGF concentration was equivalent. These data sug gest that the activity of proteolytic processing may be also an important f actor for the expression of the biological function of HGF.