INCREASED TRANSFORMING GROWTH FACTOR-BETA-1 GENE-EXPRESSION IN HUMAN LIVER-DISEASE

We recently demonstrated that transforming growth factor-beta-1 stimulates collagen synthesis in hepatic cells in vitro, and that the synthesis of this cytokine is markedly increased in two rodent models of hepatic fibrosis. In the present study, we investigated the association of transforming growth factor-beta-1 (TFG-beta-1) gene expression in human liver disease. Sixteen patients with active liver disease had percutaneous liver biopsies performed for diagnostic purposes. Total RNA was extracted from an unused portion of each biopsy and then subjected to hybridization analysis with the following human cDNA clones: albumin, pro-alpha-1 (I) collagen, and TGF-beta-1. Surgical liver biopsy specimens from two patients without hepatic disease were used as controls. When compared to controls, the patients with active liver disease had a 19% decrease in albumin, a 97% increase in type I collagen, and a 120% increase in transforming growth factor-beta-1 mRNA levels. Moreover, steady-state levels of TGF-beta-1 and procollagen mRNAs were significantly correlated. Nuclear run-on assays showed that livers from two patients with fibrosis had TGF-beta-1 transcription rates that were more than 2-fold higher than rates in control livers. These findings indicate that transforming growth factor-beta-1 gene expression is significantly enhanced in man during active liver disease.