title: B7-1 Is Not Induced in Podocytes of Human and Experimental Diabetic Nephropathy.
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.
authors: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy;
authors: Elena
authors: E
authors: Gagliardini
authors: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy;
authors: Rubina
authors: R
authors: Novelli
authors: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy;
authors: Daniela
authors: D
authors: Corna
authors: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy;
authors: Carlamaria
authors: C
authors: Zoja
authors: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy;
authors: Barbara
authors: B
authors: Ruggiero
authors: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy; ariela.benigni@marionegri.it.
authors: Ariela
authors: A
authors: Benigni
authors: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy; Unit of Nephrology and Dialysis, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy; and Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.
authors: Giuseppe
authors: G
authors: Remuzzi
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000032:analysis / Q000096:biosynthesis*; D003928:Diabetic Nephropathies / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D050199:Podocytes / Q000737:chemistry / Q000378:metabolism*
chemical_list: D018122:B7-1 Antigen
keywords: B7–1; diabetic nephropathy; podocyte