TRANSFORMING GROWTH-FACTOR-BETA-1 REGULATES PLATELET-DERIVED GROWTH-FACTOR RECEPTOR-BETA SUBUNIT IN HUMAN LIVER FAT-STORING CELLS

Activated liver fat-storing cells (FSC) are known to play a key role i n the development of liver fibrosis, An important element in FSC activ ation process is the increased expression of receptors for platelet-de rived growth factor (PDGF), a potent mitogen for FSC. The aim of the p resent study was to evaluate the expression PDGF-receptor alpha and be ta subunits in cultured human FSC and their regulation induced by tran sforming growth factor-beta 1 (TGF-beta), a cytokine potentially invol ved in an autocrine loop. TGF-beta induced a significant increase of t he mitogenic effect of PDGF-BB and did not affect the mitogenicity of PDGF-AA and PDGF-AB, suggesting a selective action of the PDGF-recepto r-beta subunit. This hypothesis was confirmed by regulation experiment s showing selective and time-dependent upregulation of the messenger ( m)RNA encoding for the PDGF-receptor-beta subunit and the relative pro tein induced by TGF-beta. In addition, binding studies showed a parall el increase of PDGF-BB binding sites after incubation of human FSC wit h TGF-beta. These studies provide evidence for an additional mechanism leading to the perpetuation of FSC activation and proliferation and c ontribute to a better understanding of the role of TGF-beta and PDGF i n the development of liver fibrosis.