Interleukin-17A blockade reduces albuminuria and kidney injury in an accelerated model of diabetic nephropathy
Diabetic nephropathy (DN) is one of the most common complications of diabetes, and currently the first end-stage renal disease worldwide. New strategies to treat DN using agents that target inflammatory pathways have attracted special interest. Recent pieces of evidences suggest a promising effect o...
| Autores: | , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Universidad Autónoma de Madrid |
| Repositorio: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.uam.es:10486/688802 |
| Acceso en línea: | http://hdl.handle.net/10486/688802 https://dx.doi.org/10.1016/ j.kint.2018.12.031 |
| Access Level: | acceso abierto |
| Palabra clave: | BTBR ob/ob Diabetic nephropathy IL-17A Inflammation Medicina |
| Sumario: | Diabetic nephropathy (DN) is one of the most common complications of diabetes, and currently the first end-stage renal disease worldwide. New strategies to treat DN using agents that target inflammatory pathways have attracted special interest. Recent pieces of evidences suggest a promising effect of IL-17A, the Th17 effector cytokine. Among experimental DN models, mouse strain BTBR ob/ob (leptin deficiency mutation) develops histological features similar to human DN, which means an opportunity to study mechanisms and novel therapies aimed at DN regression. We found that BTBR ob/ob mice presented renal activation of the factors controlling Th17 differentiation. The presence of IL-17A-expressing cells, mainly CD4D and gd lymphocytes, was associated with upregulation of proinflammatory factors, macrophage infiltration and the beginning of renal damage. To study IL-17A involvement in experimental DN pathogenesis, treatment with an IL-17A neutralizing antibody was carried out starting when the renal damage had already appeared. IL-17A blockade ameliorated renal dysfunction and disease progression in BTBR ob/ob mice. These beneficial effects correlated to podocyte number restoration and inhibition of NF-kB/ proinflammatory factors linked to a decrease in renal inflammatory-cell infiltration. These data demonstrate that IL-17A takes part in diabetes-mediated renal damage and could be a promising therapeutic target to improve DN. |
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