EXPRESSION OF HEPATOCYTE GROWTH-FACTOR, TRANSFORMING GROWTH-FACTOR-ALPHA, AND TRANSFORMING GROWTH-FACTOR BETA(1) MESSENGER-RNA IN VARIOUS HUMAN LIVER-DISEASES AND CORRELATION WITH HEPATOCYTE PROLIFERATION

Hepatocyte growth factor (HGF) and transforming growth factor alpha (T GF-alpha) stimulate liver regeneration, whereas transforming growth fa ctor beta(1) (TGF-beta(1)) inhibits it in rats, However their signific ance in human liver diseases, especially in severe acute liver injury, remains unclear. We studied HGF, TGF-alpha, and TGF-beta(1) messenger RNA (mRNA) expression in the livers of patients with Liver diseases u sing a competitive reverse transcriptase polymerase chain reaction, As little as a twofold difference in mRNA expression could be detected f rom minute liver biopsy samples, We then examined cell proliferation u sing proliferating cell nuclear antigen (PCNA) staining, HGF mRNA leve ls were significantly higher (approximately threefold) in acute hepati tis (AH) than in exacerbation of chronic liver disease (EX) (P < .05). TGF-alpha mRNA levels were significantly greater in AH (approximately twofold) than EX (P < .05), and the levels were significantly higher (approximately threefold) in chronic hepatitis (CH) than in EX (P < .0 5), The TGF-beta(1) mRNA levels in all the groups were not significant ly different, In acute liver injury (AH and EX), there was a significa nt correlation between HGF mRNA expression and the PCNA labeling index (LI) in the liver (r = .87, P < .0005), TGF-alpha mRNA expression als o correlated with the PCNA LI (r = .92, P < .0001), There was no signi ficant correlation between the serum HGF and the PCNA LI in the liver. In conclusion, HGF and TGF-alpha produced in the liver stimulate hepa tocyte proliferation in response to acute liver injury in humans.