Loss of diacylglycerol kinase epsilon in mice causes endothelial distress and impairs glomerular Cox-2 and PGE2 production.

Loss of diacylglycerol kinase epsilon in mice causes endothelial distress and impairs glomerular Cox-2 and PGE2 production. Am J Physiol Renal Physiol. 2016 Feb 17;:ajprenal.00431.2015 Authors: Zhu J, Chaki M, Lu D, Ren C, Wang SS, Rauhauser AA, Li B, Zimmerman S, Jun B, Du Y, Vadnagara K, Wang H, Elhadi S, Quigg RJ, Topham MK, Mohan C, Ozaltin F, Zhou XJ, Marciano DK, Bazan NG, Attanasio M Abstract Thrombotic microangiopathy (TMA) is a disorder characterized by microvascular occlusion that can lead to thrombocytopenia, hemolytic anemia and glomerular damage. Complement activation is the central event in most cases of TMA. Primary forms of TMA are caused by mutations in genes encoding components of the complement or regulators of the complement cascade. Recently, we and others have described a genetic form of TMA caused by mutations in the gene diacylglycerol kinase epsilon (DGKE) that encodes the lipid kinase DGKε. DGKε is unrelated to the complement pathway, which suggests that unidentified pathogenic mechanisms independent of complement dysregulation may result in TMA. Studying Dgke knockout mice may help to understand the pathogenesis of this disease, but no glomerular phenotype has been described in these animals so far. Here we report that Dgke null mice present subclinical microscopic anomalies of the glomerular endothelium and basal membrane that worsen with age, and develop glomerular capillary occlusion when exposed to ne...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research