Elevated cannabinoid receptor 1 and G protein-coupled receptor 55 expression in proximal tubule cells and whole kidney exposed to diabetic conditions

Abstract

Hyperglycaemia increases the risk of developing diabetic nephropathy, with primary targets in the glomerulus and proximal tubule. Importantly, glomerular damage in the kidney leads to elevated albumin levels in the filtrate, which contributes to tubular structural modifications that lead to dysfunction. Diabetes alters the endocannabinoid system in a number of target organs, with previous research characterizing tissue-specific changes in the expression of the cannabinoid receptor 1 (CB1 ) and G protein-coupled receptor 55 (GPR55), a putative cannabinoid receptor, in diabetes. Although these receptors have a functional role in the cannabinoid system in the kidney, there has been little investigation into changes in the expression of CB1 and GPR55 in the proximal tubule under diabetic conditions. In this study, CB1 and GPR55 messenger RNA and protein levels were quantified in cultured human kidney cells and then treated with either elevated glucose, elevated albumin, or a combination of glucose and albumin for 4, 6, 18, or 24 h. In addition, CB1 and GPR55 protein expression was characterized in whole-kidney lysate from streptozotocin-induced diabetic Sprague-Dawley rats. In vitro exposure to elevated glucose and albumin increased CB1 and GPR55 messenger RNA and protein expression in proximal tubule cells in a time-dependant manner. In whole kidney of streptozotocin-induced diabetic rats, CB1 protein was upregulated, whereas GPR55 protein concentration was not altered. Thus, expression of CB1 and GPR55 in proximal tubules is altered in response to elevated levels of glucose and albumin. Further investigations should determine if these receptors are effective physiological targets for the treatment and prevention of diabetic nephropathy.

Keywords: G protein-coupled receptor 55; albumin; cannabinoid; cannabinoid receptor 1; diabetes; glucose; kidney; proximal tubule.