Transforming growth factor-β1 regulates platelet-derived growth factor receptor β subunit in human liver fat-storing cells

✍ Scribed by Massimo Pinzani; Alessandra Gentilini; Alessandra Caligiuri; Raffaella De Franco; Giulia Pellegrini; Stefano Milani; Fabio Marra; Paolo Gentilini

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 901 KB
• Volume: 21
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840210136

✦ Synopsis

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-Pl (TGF-P), a cytokine potentially involved in an autocrine loop. TGF-P 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-P subunit. This hypothesis was confirmed by regulation experiments showing selective and time-dependent upregulation of the messenger (m)RNA encoding for the PDGF-receptor$ subunit and the relative protein induced by TGF-P. In addition, binding studies showed a parallel increase of PDGF-BB binding sites after incubation of human FSC with TGF-P. 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-