Cannabinoid Receptor 1 Inhibition in Chronic Kidney Disease: A New Therapeutic Toolbox
We and others demonstrated that renal CB1R expression was increased in diabetic nephropathy, both in humans (12, 45) and rodents (14, 15, 17, 18). CB1R Activation Promotes Non-Metabolic Renal Fibrosis So far, only our group studied the role of CB1R in an experimental model of non-metabolic renal fibrosis in vivo in mice (12) (Figure 3). Interestingly, iNOS overactivity was also found to contribute to renal fibrosis in UUO, a non-metabolic experimental model of renal fibrosis (192). In addition, recent studies highlighted that CB1R also promotes renal fibrosis in non-metabolic nephropathies and that its inhibition reduced the development of renal fibrosis. Abbreviations 2-AG, 2-arachidonoylglycerol; ACC, acetyl-CoA carboxylase; AEA, anandamide; AMPK, AMP-activated kinase; Ang II, angiotensin II; AT1, Ang II type 1 receptors; BBB, blood brain barrier; BP, blood pressure; CAD, chronic kidney allograft dysfunction; CB1R, cannabinoid receptor type 1; CB2R, cannabinoid receptor type 1; CCR2, CC chemokine receptor 2; CKD, chronic kidney disease; COX-2, cyclooxygenase type 2; DAGL, sn-1-specific diacylglycerol lipase; ECS, endocannabinoid system; ESRD, end-stage renal disease; FAAH, fatty acid amide hydrolase; GFR, glomerular filtration rate; GLUT2, glucose transporter 2; HK2, human proximal tubular cell line; HP, hemopressin; HTN, hypertension; IHC, immunohistochemical assay; LKB1, tumor suppressor liver kinase B1; MAGL, monoacylglycerol lipase; MCP-1, monocyte chemoattractant protein-1; NAPE, N-arachidonoyl phosphatidyl ethanolamine; NAPE-PLD, NAPE-specific phospholipase D; PIP2, 2-arachidonoyl-phosphatidylinositol 4,5-bisphosphate; PKA, protein kinase A; PKC, protein kinase C; RAS, renin angiotensin system; SGLT2, sodium glucose co-transporter 2; SHR, spontaneously hypertensive rat; RPTC, renal proximal tubular epithelial cells; RT-PCR, Reverse transcription and polymerase chain reaction; SR141716A, rimonabant; STZ, streptozotocin; TAL, thick ascending limb; THC, tetrahydrocannabinol; TGFβ, transforming growth factor β; TRPV1, transient receptor potential vanilloid type I channels; UUO, unilateral ureteral obstruction; WB, western blot; WIN, WIN55,212-2; ZDF, Zucker diabetic fatty.
Tags:
- Cannabinoid receptor 2
- Cannabinoid receptor 1
- Endocannabinoid system
- 2-Arachidonoylglycerol
- Chronic kidney disease
- Diabetic nephropathy
- Angiotensin
- Angiotensin II receptor type 1
- Kidney
- Cannabinoid
- Nephron
- TRPV1
- Fatty-acid amide hydrolase 1
- Arteriole
- Receptor (biochemistry)
- Cell biology
- Biochemistry