Angiogenesis and Inflammation in Chronic Pancreatitis: Modulatory Role of CD39, the Vascular Ectonucleotidase

• Applicant: Dr. Beat Martin Künzli
• Subject Area: General and Visceral Surgery
• Term: from 2004 to 2006
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5441631

Extracellular nucleotides activate specific purinergic-type 2 (P2) receptors and associated signaling proteins to trigger inflammatory reactions. Ectonucleotidases (e.g. CD39) hydrolyze these mediators and, in concert with P2-receptors appear to play a critical role in mediating inflammation, angiogenesis and fibrogenesis. We will investigate these inter-related mechanisms in chronic pancreatitis using both human clinical samples and an animal model studying mice null for cd39, the dominant vascular ectonucleotidase. Specific aim 1. To identify and describe distribution of CD39 and P2-receptors in tissue biopsies from human normal pancreas, pancreatitis and pancreatic cancer. Specific aim 2. To study the development of chronic inflammation and fibrogenesis in cd39-null mice with experimental pancreatitis. Specific aim 3. To evaluate neo-angiogenesis in cd39-null mice with experimental pancreatitis. Specific aim 4. To study the significance and interconnection of CD39, P2Y2 and selected related metalloproteinases (MMP-1, -2, -9) with guanylate binding protein-1 (GBP-1) in cell experiments in vitro. These experiments will elucidate for the first time the potential role of ectonucleotidases and purinergic signaling (NTPDases, e.g. CD39) in angiogenesis and chronic inflammation and therefore provide a better understanding of the pathogenesis of chronic pancreatitis.

• DFG Programme: Research Fellowships