Abstract: FR-PO985
Evaluation of CB1 Receptor Expression in Human Diabetic Kidney Disease and Rodent CKD Models
Session Information
- Pathology and Lab Medicine: Basic
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pathology and Lab Medicine
- 1601 Pathology and Lab Medicine: Basic
Authors
- Ma, Li-Jun, Janssen R&D, Johnson & Johnson, Spring House, Pennsylvania, United States
- Rankin, Matthew M., Janssen R&D, Johnson & Johnson, Spring House, Pennsylvania, United States
- Ma, Jing ying, Janssen R & D, Johnson & Johnson, Spring House, Pennsylvania, United States
- Wallace, Nathaniel Hawthorne, Janssen R&D, Johnson & Johnson, Spring House, Pennsylvania, United States
- Rady, Brian, Janssen R&D, Johnson & Johnson, Spring House, Pennsylvania, United States
- Li, Jingjun, Janssen R&D, Johnson & Johnson, Spring House, Pennsylvania, United States
- Bennet, Bindu, Janssen R & D, Johnson & Johnson, Spring House, Pennsylvania, United States
- Carreira, Vinicius Soares, Janssen R & D, Johnson & Johnson, Spring House, Pennsylvania, United States
- Tam, Joseph, Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
- Pocai, Alessandro, Janssen R&D, Johnson & Johnson, Spring House, Pennsylvania, United States
- Nawrocki, Andrea R., Janssen R&D, Johnson & Johnson, Spring House, Pennsylvania, United States
Background
Published data suggest that cannabinoid receptor 1 (CB1R) is an attractive target for metabolic complications, including renal fibrosis and diabetic kidney disease (DKD). CB1R protein, detected by immunohistochemistry, was reported to be expressed at low level in normal kidneys from human and rodents, and increased in renal biopsy samples from patients with DKD and fibrotic kidneys in rodents. Elevated expression of CB1R is postulated to be implicated in DKD leading to metabolic derangement, inflammation and fibrosis. We aimed to characterize CB1R protein expression in human DKD and three rodent chronic kidney disease (CKD) models.
Methods
Histological sections of renal biopsies from DKD patients and autopsy samples from normal human subjects were analyzed by immunohistochemistry to assess CB1R protein expression. Rodent CKD models included subtotal nephrectomy (STNx, on 129/Sv), unilateral ureteral obstruction (UUO, on C57BL/6) and folic acid nephropathy (FAN, on C57BL/6). Paraffin sections of kidney from normal control and diseased groups from each model (12 weeks after surgery for STNx, 10 days after surgery for UUO, 6 weeks after folic acid injection for FAN) were evaluated. Anti-CB1R polyclonal antibody from ImmunoGenes (Hungary) was used for all immunohistochemistry. Sections from human brain and mouse tissues (brain, kidney) from CB1R wild type (WT) and knockout (KO) were used as positive or negative control.
Results
Specific CB1R protein expression was observed in the presynaptic axons in the human and mouse brains without non-specific background. CB1R labeling was absent in the CB1R KO brain and kidneys. No specific CB1R positive labeling was observed in the normal mouse kidneys, normal human kidneys, or renal biopsy samples from human DKD. Only minimal and focal (less than 5% of total kidney area) CB1R protein expression was observed in tubular epithelial cells in the kidneys from STNx, UUO, and FAN models.
Conclusion
CB1R protein expression was absent from normal and human DKD, and very low and only minimally and focally increased in diseased kidneys from rodent CKD models. These observations suggest challenges for validation of this target in renal fibrosis and diabetic kidney disease.
Funding
- Commercial Support –