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B7-1 Is Not Induced in Podocytes of Human and Experimental Diabetic Nephropathy
Elena Gagliardini1, Rubina Novelli1, Daniela Corna1
1IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy;
Abstract:
The incidence of progressive kidney disease associated with diabetes continues to rise worldwide. Current standard therapy with angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers achieves only partial renoprotection, increasing the need for novel therapeutic approaches. Previous studies described B7-1 induction in podocytes of patients with proteinuria, including those with FSGS and type 2 diabetic nephropathy (DN). These findings sparked great excitement in the renal community, implying that abatacept, a costimulatory inhibitor that targets B7-1, could be a novel therapy for diabetic renal disease. Given previous concerns over the value of B7-1 immunostaining and the efficacy of abatacept in patients with recurrent FSGS after renal transplantation, we investigated B7-1 expression in human and experimental DN before embarking on clinical studies of the use of B7-1 targeting strategies to treat proteinuria in DN. Immunohistochemical analysis of kidney specimens using different antibodies revealed that B7-1 is not induced in podocytes of patients with DN, independent of disease stage, or BTBR ob/obmice, a model of type 2 diabetes. These results do not support the use of abatacept as a therapeutic strategy for targeting podocyte B7-1 for the prevention or treatment of DN.
Insights
B7-1 is not induced in the kidneys of patients with diabetic nephropathy (DN). This finding does not support using abatacept to target B7-1 for treating DN, despite previous suggestions for this approach.
Area of Science:
- Nephrology
- Immunology
- Diabetology
Background:
- Diabetic nephropathy (DN) incidence is rising globally, with current therapies offering incomplete kidney protection.
- Novel therapeutic strategies are crucial for managing progressive kidney disease in diabetes.
- Previous research suggested B7-1 induction in podocytes could make abatacept a potential DN therapy.
Purpose of the Study:
- To investigate B7-1 expression in human and experimental diabetic nephropathy (DN).
- To evaluate the potential of targeting podocyte B7-1 for DN treatment.
- To determine if abatacept is a viable therapeutic strategy for DN.
Main Methods:
- Immunohistochemical analysis of kidney specimens from patients with DN and BTBR ob/ob mice (a type 2 diabetes model).
- Utilized various antibodies to detect B7-1 expression.
- Evaluated B7-1 expression independent of disease stage in human DN.
Main Results:
- B7-1 was not found to be induced in the podocytes of patients with DN, regardless of disease stage.
- B7-1 expression was also not observed in BTBR ob/ob mice, a model for type 2 diabetes.
- These findings contradict previous assumptions about B7-1 in DN.
Conclusions:
- The study does not support the use of abatacept for targeting podocyte B7-1 in the prevention or treatment of diabetic nephropathy (DN).
- Further research into alternative therapeutic strategies for DN is warranted.
- The efficacy of targeting B7-1 in DN requires re-evaluation based on these findings.
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