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

doi:10.1016/0270-9139(95)90433-6

Hepatology

Volume 21, Issue 1, January 1995, Pages 232-239

https://doi.org/10.1016/0270-9139(95)90433-6 Get rights and content

Abstract

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.

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TGF beta-1 was also found to stimulate rat mesangial cell proliferation in long-term cultures associated with upregulation of the PDGFR-β and enhanced synthesis of the PDGF B polypeptide (Haberstroh et al., 1993). Similarly, Pinzani and coworkers (1995) found that TGF beta-1 selectively upregulated PDGFR-β mRNA in human fat storing cells. Other investigators reported that TGF beta-1 downregulated the PDGFR-α mRNA and protein in human lung fibroblasts in vitro (Bonner et al., 1995).
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^☆: This work was supported by a grant from Ministero dell'Universita e della Ricerca Scientifica e Tecnologica-Progetto Nazionale Cirrosi Epatica ed Epatiti Virali (Rome, Italy). Financial support was also provided by Fondazione Italiana per lo Studio del Fegato (Italian Liver Foundation, Florence, Italy)

^☆☆: Portions of this work were presented at the 28th Annual Meeting of the European Association for the Study of the Liver, Paris, France, September 1–4, 1993, and published in abstract form (J Hepatol 1993; 18: S13).

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

Abstract

Lancet

Exp Cell Res

Gastroenterology

Biochem Biophys Res Comm

J Biol Chem

Anal Biochem

J Biol Chem

Cell

J Hepatol

J Biol Chem

J Biol Chem

J Biol Chem

Extracellular matrix gene expression increases preferentially in rat lipocytes and sinusoidal endothelial cells during hepatic fibrosis in vivo

J Clin Invest

In situ hybridization for procollagen types I, III and IV mRNA in normal and fibrotic rat liver: evidence for predominant expression in nonparenchymal liver cells

Hepatology

Cellular localization of laminin gene transcripts in normal and fibrotic human liver

Am J Pathol

The cellular basis of hepatic fibrosis

Lipocytes and transitional cells in alcoholic liver disease: a morphometric study

Hepatology

Immunohystochemical detection of proliferating lipocytes in regenerating liver

J Pathol

Role of mesenchymal cell populations in porcine serum-induced rat liver fibrosis

Hepatology

Activation of cultured rat hepatic lipocytes by Kupffer cell conditioned medium: direct enhancement of matrix synthesis and stimulation of cell proliferation via induction of platelet-derived growth factor receptors

J Clin Invest

Structural and functional studies on platelet-derived growth factor

EMBO J