Platelet-derived growth factor receptor-ß signaling in the pathogenesis of liver fibrosis

• Applicant: Dr. Monika Krampert
• Subject Area: Public Health, Healthcare Research, Social and Occupational Medicine
• Term: from 2005 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 16871850

Liver fibrosis, caused by viral hepatitis, alcohol abuse or other noxae is a worldwide socio-economic problem. Thus, understanding the mechanisms involved in the pathogenesis of fibrosis will help to identify therapeutic targets to slow down or even prevent its progression. Platelet-derived growth factor (PDGF) has been identified as a central player in the early phase of liver fibrosis, especially in the activation of hepatic stellate cells, the major fibrogenic cell type of the liver. The proposed project aims to investigate the role of platelet-derived growth factor receptor signaling pathways in an induced model of liver fibrosis using mice harboring either an activating, or a pathwayrestricting mutation of the platelet-derived growth factor receptor-ß. Besides a detailed study of the induction and progression of liver fibrosis in these mice, isolated hepatic stellate cells from wild-type and mutant mice will be used for analysis of the PDGF receptor signaling pathways, and to study the influence of the receptor mutations on stellate cell activation, proliferation and chemotaxis. In addition, we aim to explore these primary cells as well as cell lines carrying the same mutations for a proteomic approach to identify novel and/or liver-specific proteins involved in PDGF signaling as possible therapeutic drug targets.

• DFG Programme: Research Fellowships
• International Connection: Sweden
• Host: Professor Dr. Carl-Henrik Heldin