Interleukin-17A blockade reduces albuminuria and kidney injury in an accelerated model of diabetic nephropathy

Lavoz C.; Matus Y.S.; Orejudo M.; Carpio J.D.; Droguett A.; Egido J.; Mezzano S.; Ruiz-Ortega M.

Abstract

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 CD4(+) and gamma delta 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-kappa B/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.

Más información

Título según WOS: Interleukin-17A blockade reduces albuminuria and kidney injury in an accelerated model of diabetic nephropathy
Título según SCOPUS: Interleukin-17A blockade reduces albuminuria and kidney injury in an accelerated model of diabetic nephropathy
Título de la Revista: KIDNEY INTERNATIONAL
Volumen: 95
Número: 6
Editorial: Elsevier Science Inc.
Fecha de publicación: 2019
Página de inicio: 1418
Página final: 1432
Idioma: English
DOI:

10.1016/j.kint.2018.12.031

Notas: ISI, SCOPUS