Novel approach to Inhibit RAGE and protect from diabetic nephropathy

Grant number: 5-2008-760 | Funding period: 2008 - 2009



This proposal will test an innovative approach to inhibit RAGE signaling by sequestering high mobility group box1 (HMGB1), an important RAGE ligand. HMGB1 has been recently demonstrated to bind the lectin-like domain of the endothelial protein thrombomodulin (TM) and this interaction prevents ligation of RAGE by HMGB1. We have developed transgenic mice that overexpress soluble lectin-like domain, which is released into the circulation. We provide supplementary evidence that the lectin-like domain is functional by demonstrating that the transgenic mice are protected from HMGB1-mediated events such as LPS-induced morbidity and renal damage from ischaemia-reperfusion injury. Using our unique tr..

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