Erforschung der Rolle von Nogo-B und seinem neu identifizierten Oberflächenrezeptor im kardiovaskulären System

• Antragsteller: Dr. Michael Schleicher
• Fachliche Zuordnung: Anatomie und Physiologie
• Förderung: Förderung von 2005 bis 2007
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 20066835

The Nogo isoforms -A, -B, and -C are transmembrane proteins which belong to the reticulon family. While Nogo-A is expressed in the central nervous system and serves as an endogenous inhibitor of axonal growth and repair, little is known about the function or significance of the other Nogo isoforms. Recent data show that Nogo-B is highly enriched in caveolae of endothelial and smooth muscle cells as well as in intact blood vessels. Nogo-B promotes migration of endothelial cells while antagonizing the migration of vascular smooth muscle cells. Unlike Nogo-A, Nogo-B thereby acts via its amino terminus. Disruption of the Nogo-A/B gene impairs the response to vascular injury and tissue ischemia resulting in an exaggerated neointimal proliferation and diminished ischemic reserve capacity. Gene transfer of Nogo-B rescues these phenotypes. In addition, a novel receptor for the amino terminus of Nogo-B has been cloned which is highly expressed in vascular cells. Thus, the hypothesis arises that Nogo-B binding to its cognate receptor is a novel regulatory system coordinating vascular response to injury or tissue ischemia. Therefore the following research objectives are proposed: 1. Definition of the role of Nogo-B during arteriogenesis and angiogenesis; 2. Characterization of the receptor for Nogo-B in vascular cells and the physiological consequences upon ligand binding. These experiments will help to define the role of Nogo-B in the vasculature and may lead to potential therapies modulating angiogenesis, arteriogenesis and vascular remodeling.

• DFG-Verfahren: Forschungsstipendien
• Internationaler Bezug: USA
• Gastgeber: Professor Dr. William C. Sessa