François Hélène, Durrbach Antoine, Beaudreuil Séverine, Charpentier Bernard, Lecru Lola
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.
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.
Nephrol Ther. 2016 Apr;12 Suppl 1:S115-22. doi: 10.1016/j.nephro.2016.02.004. Epub 2016 Mar 8.
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.
慢性肾脏病仍然是公共卫生系统面临的一项重大挑战，它对应着肾功能性组织被细胞外基质蛋白（如胶原蛋白和纤连蛋白）所取代的过程。迄今为止，除了肾脏保护策略外，尚无针对慢性肾脏病的有效治疗方法。大麻素系统，尤其是大麻素受体1（CB1）和2（CB2），可能成为慢性肾脏病的一个新的治疗靶点。在糖尿病和肥胖模型中获得的实验数据表明，阻断CB1和刺激CB2可能减缓糖尿病肾病的发展。在人类肾脏中，CB1在各种慢性肾病中的表达增加，且与肾功能相关。此外，内源性CB1和CB2配体在肾脏纤维化形成过程中大幅增加。在肾脏纤维化的实验模型中进行的微阵列分析发现，编码CB1受体的基因是上调最为明显的基因之一。我们还证明，在实验模型中，通过涉及成肌纤维细胞（肾脏纤维化过程中的主要效应细胞）上的CB1的直接机制，抑制CB1和刺激CB2可减少肾脏纤维化形成。因此，CB1阻滞剂可能成为慢性肾脏病和糖尿病的一种新型治疗靶点。
