Transforming growth factor-beta 1 regulates platelet-derived growth factor receptor beta subunit in human liver...

Activated liver fat-storing cells (FSC) are known to play a key role in the development of liver fibrosis. An important element in FSC activation process is the increased expression of receptors for platelet-derived growth factor (PDGF), a potent mitogen for FSC. The aim of the present study was to evaluate the expression PDGF-receptor alpha and beta subunits in cultured human FSC and their regulation induced by transforming growth factor-beta 1 (TGF-beta), a cytokine potentially involved in an autocrine loop. TGF-beta induced a significant increase of the mitogenic effect of PDGF-BB and did not affect the mitogenicity of PDGF-AA and PDGF-AB, suggesting a selective action of the PDGF-receptor-beta subunit. This hypothesis was confirmed by regulation experiments showing selective and time-dependent upregulation of the messenger (m)RNA encoding for the PDGF-receptor-beta subunit and the relative protein induced by TGF-beta. In addition, binding studies showed a parallel increase of PDGF-BB binding sites after incubation of human FSC with TGF-beta. These studies provide evidence for an additional mechanism leading to the perpetuation of FSC activation and proliferation and contribute to a better understanding of the role of TGF-beta and PDGF in the development of liver fibrosis.