title: [Role of cannabinoid receptors in renal diseases].
abstract: 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.
authors.affiliation: Inserm unité 1197, interactions cellules souches-niches : physiologie, tumeurs et réparation tissulaire, 12, avenue Paul-Vaillant-Couturier, 94800 Villejuif, France; Institut André Lwoff, hôpital Paul-Brousse, 12, avenue Paul-Vaillant-Couturier, 94800 Villejuif, France; Service de néphrologie, dialyse et transplantation, hôpital Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France; Institut francilien de recherche en néphrologie et transplantation, 78, rue du Général-Leclerc, 94270 Le Kremlin-Bicêtre, France. Electronic address: helene.francois@aphp.fr.
authors.forename: Hélène
authors.initials: H
authors.lastname: François
authors.affiliation: Inserm unité 1197, interactions cellules souches-niches : physiologie, tumeurs et réparation tissulaire, 12, avenue Paul-Vaillant-Couturier, 94800 Villejuif, France; Institut André Lwoff, hôpital Paul-Brousse, 12, avenue Paul-Vaillant-Couturier, 94800 Villejuif, France; Service de néphrologie, dialyse et transplantation, hôpital Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France; Institut francilien de recherche en néphrologie et transplantation, 78, rue du Général-Leclerc, 94270 Le Kremlin-Bicêtre, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Durrbach
authors.affiliation: Inserm unité 1197, interactions cellules souches-niches : physiologie, tumeurs et réparation tissulaire, 12, avenue Paul-Vaillant-Couturier, 94800 Villejuif, France; Institut André Lwoff, hôpital Paul-Brousse, 12, avenue Paul-Vaillant-Couturier, 94800 Villejuif, France; Service de néphrologie, dialyse et transplantation, hôpital Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France; Institut francilien de recherche en néphrologie et transplantation, 78, rue du Général-Leclerc, 94270 Le Kremlin-Bicêtre, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Beaudreuil
authors.affiliation: Inserm unité 1197, interactions cellules souches-niches : physiologie, tumeurs et réparation tissulaire, 12, avenue Paul-Vaillant-Couturier, 94800 Villejuif, France; Institut André Lwoff, hôpital Paul-Brousse, 12, avenue Paul-Vaillant-Couturier, 94800 Villejuif, France; Service de néphrologie, dialyse et transplantation, hôpital Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France; Institut francilien de recherche en néphrologie et transplantation, 78, rue du Général-Leclerc, 94270 Le Kremlin-Bicêtre, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Charpentier
authors.affiliation: Inserm unité 1197, interactions cellules souches-niches : physiologie, tumeurs et réparation tissulaire, 12, avenue Paul-Vaillant-Couturier, 94800 Villejuif, France; Institut André Lwoff, hôpital Paul-Brousse, 12, avenue Paul-Vaillant-Couturier, 94800 Villejuif, France; Service de néphrologie, dialyse et transplantation, hôpital Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France; Institut francilien de recherche en néphrologie et transplantation, 78, rue du Général-Leclerc, 94270 Le Kremlin-Bicêtre, France.
authors.forename: Lola
authors.initials: L
authors.lastname: Lecru
mesh_terms: D000818:Animals; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D058628:Myofibroblasts / Q000187:drug effects; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000378:metabolism; D043882:Receptors, Cannabinoid / Q000627:therapeutic use; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid
keywords: Cannabinoid receptor; Chronic kidney disease; Diabetes; Diabète; Fibrose rénale; Insuffisance rénale chronique; Renal fibrosis; Récepteur cannabinoïde