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Transforming growth factor‐β1 regulates platelet‐derived growth factor receptor β subunit in human liver fat‐storing cells
Author(s) -
Pinzani Massimo,
Gentilini Alessandra,
Caligiuri Alessandra,
De Franco Raffaella,
Pellegrini Giulia,
Milani Stefano,
Marra Fabio,
Gentilini Paolo
Publication year - 1995
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840210136
Subject(s) - platelet derived growth factor receptor , autocrine signalling , growth factor , platelet derived growth factor , biology , receptor , transforming growth factor beta , cytokine , microbiology and biotechnology , downregulation and upregulation , transforming growth factor , growth factor receptor , endocrinology , medicine , signal transduction , immunology , biochemistry , gene
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‐β1 (TGF‐β), a cytokine potentially involved in an autocrine loop. TGF‐β 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‐β subunit. This hypothesis was confirmed by regulation experiments showing selective and time‐dependent upregulation of the messenger (m)RNA encoding for the PDGF‐receptor‐β subunit and the relative protein induced by TGF‐β. In addition, binding studies showed a parallel increase of PDGF‐BB binding sites after incubation of human FSC with TGF‐β. 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‐β and PDGF in the development of liver fibrosis. (Hepatology 1995;21:232–239).