[Role of cannabinoid receptors in renal diseases]

Chronic kidney disease remains a major challenge for public health systems and corresponds to the replacement of renal functional tissue by extracellular matrix proteins such as collagens and fibronectin. There is no efficient treatment to date for chronic kidney disease except nephroprotective strategies. The cannabinoid system and more specifically the cannabinoid receptors 1 (CB1) and 2 (CB2) may represent a new therapeutic target in chronic kidney disease. Experimental data obtained in models of diabetes and obesity suggested that CB1 blockade and CB2 stimulation may slow the development of diabetic nephropathy. In human kidneys, CB1 expression is increased in various chronic nephropathies and correlates with renal function. Moreover, endogenous CB1 and CB2 ligands are greatly increased during renal fibrogenesis. A microarray analysis performed in an experimental model of renal fibrosis found that the gene encoding for the CB1 receptor was among the most upregulated genes. We also demonstrated that renal fibrogenesis could be reduced by CB1 inhibition and CB2 stimulation in an experimental model through a direct mechanism involving CB1 on myofibroblasts, which are the major effector cells during renal fibrosis. Therefore, CB1 blockers may represent a novel therapeutic target in chronic kidney disease and diabetes.