Academic Journal
Role of podocyte B7-1 in diabetic nephropathy
| العنوان: | Role of podocyte B7-1 in diabetic nephropathy |
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| المؤلفون: | P. Fiorina, A. Vergani, R. Bassi, M. A. Niewczas, M. M. Altintas, M. G. Pezzolesi, M. Chin, S. Tezza, M. B. Nasr, D. Mattinzoli, M. Ikehata, D. Corradi, V. Schumacher, L. Buvall, C. Yu, J. Chang, S. La Rosa, G. Finzi, A. Solini, F. Vincenti, M. P. Rastaldi, J. Reiser, A. S. Krolewski, P. H. Mundel, M. H. Sayegh, F. D'Addio |
| المساهمون: | P. Fiorina, A. Vergani, R. Bassi, M.A. Niewcza, M.M. Altinta, M.G. Pezzolesi, F. D'Addio, M. Chin, S. Tezza, M.B. Nasr, D. Mattinzoli, M. Ikehata, D. Corradi, V. Schumacher, L. Buvall, C. Yu, J. Chang, S. La Rosa, G. Finzi, A. Solini, F. Vincenti, M.P. Rastaldi, J. Reiser, A.S. Krolewski, P.H. Mundel, M.H. Sayegh |
| بيانات النشر: | American Society of Nephrology |
| سنة النشر: | 2014 |
| المجموعة: | The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| مصطلحات موضوعية: | Adult, Aged, Animal, Antigens, CD80, Diabetes Mellitus, Type 1, Diabetic Nephropathie, Female, Human, Male, Mice, Inbred C57BL, Middle Aged, Up-Regulation, Podocyte, Nephrology, Medicine (all), Settore MED/13 - Endocrinologia |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/24676639; info:eu-repo/semantics/altIdentifier/wos/WOS:000338176500009; volume:25; issue:7; firstpage:1415; lastpage:1429; numberofpages:15; journal:JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY; http://hdl.handle.net/2434/484534; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84907188863; http://jasn.asnjournals.org/content/25/7/1415.full.pdf+html |
| DOI: | 10.1681/ASN.2013050518 |
| الاتاحة: | http://hdl.handle.net/2434/484534 https://doi.org/10.1681/ASN.2013050518 http://jasn.asnjournals.org/content/25/7/1415.full.pdf+html |
| Rights: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.1BBA6ECD |
| قاعدة البيانات: | BASE |
| DOI: | 10.1681/ASN.2013050518 |
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