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 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...

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Published in:Hepatology (Baltimore, Md.) Md.), 1995-01, Vol.21 (1), p.232-239
Main Authors: Pinzani, M, Gentilini, A, Caligiuri, A, De Franco, R, Pellegrini, G, Milani, S, Marra, F, Gentilini, P
Format: Article
Language:English
Subjects:
Cells, Cultured
Humans
Lipid Metabolism
Liver - cytology
Liver - metabolism
Mitogens - pharmacology
Platelet-Derived Growth Factor - classification
Platelet-Derived Growth Factor - pharmacology
Proto-Oncogene Proteins c-sis
Receptors, Platelet-Derived Growth Factor - classification
Receptors, Platelet-Derived Growth Factor - genetics
Receptors, Platelet-Derived Growth Factor - metabolism
RNA, Messenger - metabolism
Transforming Growth Factor beta - pharmacology
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Summary: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.
ISSN:0270-9139
DOI:10.1002/hep.1840210136