DETECTION OF ACTIVITY IN THE CONDITIONED MEDIUM OF ETHANOL-TREATED HEPG2 CELLS WHICH STIMULATES COLLAGEN-SYNTHESIS IN IMR-90 CELLS

Hepatic fibrosis often occurs in alcoholic liver diseases without acco mpanying tissue necrosis or inflammation. However, the precise mechani sm of this fibrosis has not been fully clarified. In the present study , using the hepatoblastoma cell line HepG2 as a model for hepatocytes, we identified a factor that stimulates collagen synthesis of fibrobla sts in a conditioned medium of HepG2 cells after treatment with ethano l. Type I procollagen peptide (PIG) in a culture of human fibroblast I MR-90 markedly increased after incubation with the conditioned medium of ethanol-treated HepG2 cells. The stimulating activity on the produc tion of PIC by IMR-90 remained after the dialysis and evaporation of t he conditioned medium of HepG2 cells, indicating this factor was not a s volatile from low molecular substances such as acetaldehyde, acetate , or lactate. The activity of this factor diminished with heat or tryp sin treatment. A gel chromatographic analysis disclosed that the molec ular weight of this factor was similar to 8000 Da. These results sugge st that a polypeptide factor secreted from HepG2 cells by treatment wi th ethanol stimulates collagen synthesis of fibroblasts.