Role of podocyte B7-1 in diabetic nephropathy.

Details

Serval ID
serval:BIB_B702111C453D
Type
Article: article from journal or magazin.
Collection
Publications
Title
Role of podocyte B7-1 in diabetic nephropathy.
Journal
Journal of the American Society of Nephrology : Jasn
Author(s)
Fiorina P., Vergani A., Bassi R., Niewczas M.A., Altintas M.M., Pezzolesi M.G., D'Addio F., Chin M., Tezza S., Ben Nasr M., Mattinzoli D., Ikehata M., Corradi D., Schumacher V., Buvall L., Yu C.C., Chang J.M., La Rosa S., Finzi G., Solini A., Vincenti F., Rastaldi M.P., Reiser J., Krolewski A.S., Mundel P.H., Sayegh M.H.
ISSN
1533-3450 (Electronic)
ISSN-L
1046-6673
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
25
Number
7
Pages
1415-1429
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
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.
Keywords
Adult, Aged, Animals, Antigens, CD80/physiology, Diabetes Mellitus, Type 1/complications, Diabetic Nephropathies/etiology, Female, Humans, Male, Mice, Mice, Inbred C57BL, Middle Aged, Podocytes, Up-Regulation
Pubmed
Web of science
Open Access
Yes
Create date
06/09/2016 12:06
Last modification date
20/08/2019 15:25
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