Expression of Hepatocyte Growth Factor, Transforming Growth Factor α, and Transforming Growth Factor β 1 Messenger Rna in Various Human Liver Diseases and Correlation With Hepatocyte Proliferation

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Abstract
Hepatocyte growth factor (HGF) and transforming growth factor α (TGF–α) stimulate liver regeneration, whereas transforming growth factor β 1 (TGF–β 1) inhibits it in rats. However their significance in human liver diseases, especially in severe acute liver injury, remains unclear. We studied HGF, TGF–α, and TGF–β 1 messenger RNA (mRNA) expression in the livers of patients with live diseases using a competitive reverse transcriptase polymerase chain reaction. As little as a twofold difference in mRNA expression could be detected from minute liver biopsy samples. We then examined cell proliferation using proliferating cell nuclear antigen (PCNA) staining. HGF mRNA levels were significantly higher (approximately threefold) in acute hepatitis (AH) than in exacerbation of chronic liver disease (EX) ( P < .05). TGF–α 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 < .05). The TGF–β 1 mRNA levels in all the groups were not significantly different. In acute liver injury (AH and EX), there was a significant correlation between HGF mRNA expression and the PCNA labeling index (LI) in the liver (r = .87, P < .0005). TGF–α mRNA expression also correlated with the PCNA LI (r = .92, P < .0001). There was no significant correlation between the serum HGF and the PCNA LI in the liver. In conclusion, HGF and TGF–α produced in the liver stimulate hepatocyte proliferation in response to acute liver injury in humans.

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