Platelet-derived growth factor C induces liver fibrosis, steatosis, and hepatocellular carcinoma
AUTOR(ES)
Campbell, Jean S.
FONTE
National Academy of Sciences
RESUMO
Members of the platelet-derived growth factor (PDGF) ligand family are known to play important roles in wound healing and fibrotic disease. We show that both transient and stable expression of PDGF-C results in the development of liver fibrosis consisting of the deposition of collagen in a pericellular and perivenular pattern that resembles human alcoholic and nonalcoholic fatty liver disease. Fibrosis in PDGF-C transgenic mice, as demonstrated by staining and hydroxyproline content, is preceded by activation and proliferation of hepatic stellate cells, as shown by collagen, α-smooth muscle actin and glial fibrillary acidic protein staining and between 8 and 12 months of age is followed by the development of liver adenomas and hepatocellular carcinomas. The hepatic expression of a number of known profibrotic genes, including type β1 TGF, PDGF receptors α and β, and tissue inhibitors of matrix metalloproteinases-1 and -2, increased by 4 weeks of age. Increased PDGF receptor α and β protein levels were associated with activation of extracellular regulated kinase-1 and -2 and protein kinase B. At 9 months of age, PDGF-C transgenic mice had enlarged livers associated with increased fibrosis, steatosis, cell dysplasia, and hepatocellular carcinomas. These studies indicate that hepatic expression of PDGF-C induces a number of profibrotic pathways, suggesting that this growth factor may act as an initiator of fibrosis. Moreover, PDGF-C transgenic mice represent a unique model for the study of hepatic fibrosis progressing to tumorigenesis.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=552940Documentos Relacionados
- Platelet-derived growth factor in idiopathic pulmonary fibrosis.
- Platelet-derived growth factor induces apoptosis in growth-arrested murine fibroblasts.
- Platelet-derived growth factor BB induces functional vascular anastomoses in vivo.
- Platelet-derived growth factor: purification and partial characterization.
- Purification of human platelet-derived growth factor.