Expression of platelet-derived growth factor and its receptor in livers of patients with chronic liver disease

Abstract

To find if platelet-derived growth factor contributes to liver fibrosis in chronic liver disease, we studied the expression of the B-chain of this cytokine and its beta-receptor in livers of patients with chronic hepatitis or cirrhosis. Seventeen patients were included in this study. Five specimens of liver tissue obtained during autopsy from subjects without liver disease were used as controls. The location of the peptides was identified by an immunohistochemical technique with monoclonal antibodies. Expression of mRNA for the B-chain was assessed by in situ hybridization. Cells stained for the B-chain and expressing its mRNA were identified as macrophages. In control tissues, only a few cells were stained. In the patients' specimens, most stained cells were in portal areas and their number increased with histologic liver damage. In intralobular areas, the stained cells were seen in regions of focal necrosis. Portal mesenchymal and perisinusoidal cells expressed beta-receptor. These cells were dense in periportal areas, where many myofibroblast-like cells were seen. These findings suggest that the B-chain of platelet-derived growth factor is released mainly by macrophages involved in inflammatory reactions. This cytokine probably acts on myofibroblast-like mesenchymal cells, and may be implicated in liver fibrosis in chronic liver disease.

Diagnosis and Quantitation of Fibrosis

“…116 Tumor necrosis factor (TNF)-␣ has been associated with liver injury in patients with alcoholic liver disease. 117 Platelet derived growth factor is up-regulated following liver injury, 118 and levels may correlate with the degree of liver injury. 119 …”

Angiogenesis in chronic inflammatory liver disease

“…91 HGF induces EC proliferation in a VEGF-dependent manner. 80,90 The expression of PDGF in macrophages and infiltrating inflammatory cells and the expression of PDGF receptors in sinusoidal and perisinusoidal cells in periportal areas are increased during chronic viral hepatitis and/or cirrhosis, 92,93 suggesting a role in the stabilization of nascent vessels 1,94 during chronic viral hepatitisassociated angiogenesis.…”

Platelet-derived growth factor receptor-α: a novel therapeutic target in human hepatocellular cancer

“…In fact, high expression of PDGFRa is detectable in a variety of tumors, such as the basal cell carcinoma, brain tumor, gastrointestinal stromal tumor, prostatic intraepithelial neoplasia, ovarian cancer, osteosarcoma, and leukemia (3, 9 -12). PDGFRh, an isomer of PDGFR, appears later in liver development and plays a role in hepatic fibrosis (13,14). PDGFRa undergoes homodimerization of two a-chains following ligand (PDGF-AA, PDGF-AB, or PDGF-CC binding; ref.…”