Role of podocyte B7-1 in diabetic nephropathy.

Autor:	Fiorina P; Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Medicine, San Raffaele Scientific Institute, Milan, Italy; paolo.fiorina@childrens.harvard.edu., Vergani A; Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Medicine, San Raffaele Scientific Institute, Milan, Italy;, Bassi R; Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Medicine, San Raffaele Scientific Institute, Milan, Italy; DiSTeBA, Universita' del Salento, Lecce, Italy;, Niewczas MA; Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts;, Altintas MM; Department of Medicine, Rush University Medical Center, Chicago, Illinois;, Pezzolesi MG; Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts;, D'Addio F; Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Medicine, San Raffaele Scientific Institute, Milan, Italy;, Chin M; Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts;, Tezza S; Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts;, Ben Nasr M; Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts;, Mattinzoli D; Renal Research Laboratory, Fondazione IRCCS Ospedale Maggiore Policlinico and Fondazione D'Amico per la Ricerca sulle Malattie Renali, Milan, Italy;, Ikehata M; Renal Research Laboratory, Fondazione IRCCS Ospedale Maggiore Policlinico and Fondazione D'Amico per la Ricerca sulle Malattie Renali, Milan, Italy;, Corradi D; Department of Biomedical, Biotechnological and Translational Sciences, Unit of Pathology, University of Parma, Parma, Italy;, Schumacher V; Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts;, Buvall L; Nephrology Division, Massachusetts General Hospital, Boston, Massachusetts;, Yu CC; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;, Chang JM; Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;, La Rosa S; Pathology Department, Ospedale di Circolo, Varese, Italy;, Finzi G; Pathology Department, Ospedale di Circolo, Varese, Italy;, Solini A; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy;, Vincenti F; Kidney Transplant Service, University of San Francisco, San Francisco, California;, Rastaldi MP; Renal Research Laboratory, Fondazione IRCCS Ospedale Maggiore Policlinico and Fondazione D'Amico per la Ricerca sulle Malattie Renali, Milan, Italy;, Reiser J; Department of Medicine, Rush University Medical Center, Chicago, Illinois;, Krolewski AS; Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts;, Mundel PH; Nephrology Division, Massachusetts General Hospital, Boston, Massachusetts;, Sayegh MH; Transplantation Research Center, Brigham and Women's Hospital, Boston, Massachusetts; and American University of Beirut, Beirut, Lebanon.
Jazyk:	angličtina
Zdroj:	Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2014 Jul; Vol. 25 (7), pp. 1415-29. Date of Electronic Publication: 2014 Mar 27.
DOI:	10.1681/ASN.2013050518
Abstrakt:	Podocyte injury and resulting albuminuria are hallmarks of diabetic nephropathy, but targeted therapies to halt or prevent these complications are currently not available. Here, we show that the immune-related molecule B7-1/CD80 is a critical mediator of podocyte injury in type 2 diabetic nephropathy. We report the induction of podocyte B7-1 in kidney biopsy specimens from patients with type 2 diabetes. Genetic and epidemiologic studies revealed the association of two single nucleotide polymorphisms at the B7-1 gene with diabetic nephropathy. Furthermore, increased levels of the soluble isoform of the B7-1 ligand CD28 correlated with the progression to ESRD in individuals with type 2 diabetes. In vitro, high glucose conditions prompted the phosphatidylinositol 3 kinase-dependent upregulation of B7-1 in podocytes, and the ectopic expression of B7-1 in podocytes increased apoptosis and induced disruption of the cytoskeleton that were reversed by the B7-1 inhibitor CTLA4-Ig. Podocyte expression of B7-1 was also induced in vivo in two murine models of diabetic nephropathy, and treatment with CTLA4-Ig prevented increased urinary albumin excretion and improved kidney pathology in these animals. Taken together, these results identify B7-1 inhibition as a potential therapeutic strategy for the prevention or treatment of diabetic nephropathy. (Copyright © 2014 by the American Society of Nephrology.)
Databáze:	MEDLINE
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