Effect of elevated glucose and albumin levels on endocannabinoid receptor expression in proximal tubule cells

Aim: To quantify the expression of endocannabinoid receptor mRNA in proximal tubule cells exposed to elevated levels of glucose and albumin. Background: Hyperglycemia has been implicated in the etiology of diabetic nephropathy, which typically leads to elevated albumin levels in the fi ltrate. We have identifi ed a role for the endocannabinoid system in renal hypertrophy, indicating that these receptors may play a role in the progression of diabetic nephropathy. To date, there has been little investigation into changes in the expression of the endocannabinoid receptors in the proximal tubule under diabetic conditions. Methods: Human kidney cell line (HK2) were treated with high glucose, high albumin, a combination of high glucose and high albumin and the level of the endocannabinoid receptors (CB1, CB2, TRPV1 and GPR55) mRNA was assessed by real time PCR. Treatment ranged from 2 to 24 hours. Results: CB1 expression remained unchanged over all time points and under all treatments. Treatment periods of 6 and 18 hours resulted in a lower expression of CB2 in high albumin and combination treatment when compared to control groups. At both 6 and 24 hour treatment periods, TRPV1 expression in cells exposed to high glucose/high albumin was higher compared to all other groups. For GPR55, treatment for 6 and 24 hours showed expression was higher in both the high glucose and the combination group, compared to control and high albumin alone. Conclusion: We have demonstrated that exposure to elevated levels of glucose and albumin alters the level of CB2, TRPV1 and GPR55 mRNA in a proximal tubule cell line. Further investigation may indicate that these receptors provide a novel target for the treatment and prevention of diabetic nephropathy.