Fcγ receptor deficiency attenuates diabetic nephropathy
Metadatos
Title:
Fcγ receptor deficiency attenuates diabetic nephropathy
Author:
López-Parra, Virginia; Mallavia, Beñat; López-Franco, Óscar; Ortiz-Muñoz, Guadalupe; Oguiza, Ainhoa; Recio, Carlota; Blanco, Julia A Parra; Nimmerjahn, F.; Egido de los Ríos, Jesús; Gómez-Guerrero, Carmen
Entity:
UAM. Departamento de Medicina
UAM Author:
Egido De Los Ríos, Jesús
Publisher:
American Society of Nephrology
Date:
2012-09-01
Citation:
10.1681/ASN.2011080822
Journal of the American Society of Nephrology 23.9 (2012): 1518–1527
ISSN:
1046-6673 (print); 2309-1518 (online)
DOI:
10.1681/ASN.2011080822
Funded by:
This study was supported by grants from Spanish Ministry of
Science (SAF2009/11794), Ministry of Health (PI10/00072, RECAVA
RD06/0014/0035), Lilly Foundation, FRIAT, and Spanish Society of
Nephrology
Editor's Version:
http://dx.doi.org/10.1681/ASN.2011080822
Subjects:
Albuminuria; Diabetes Mellitus; Diabetic Nephropathies; Hypertrophy; Medicina
Rights:
© 2012 by the American Society of Nephrology
Abstract:
Among patients with diabetes, increased production of immunoglobulins against proteins modified by
diabetes is associated with proteinuria and cardiovascular risk, suggesting that immune mechanisms may
contribute to the development of diabetes complications, such as nephropathy. We investigated the
contribution of IgG Fcg receptors to diabetic renal injury in hyperglycemic, hypercholesterolemic mice.
Weused streptozotocin to induce diabetes in apolipoprotein E–deficientmice and in mice deficient in both
apolipoprotein E and g-chain, the common subunit of activating Fcg receptors. After 15 weeks, the mice
lacking Fcg receptors had significantly less albuminuria and renal hypertrophy, despite similar degrees of
hyperglycemia and hypercholesterolemia, immunoglobulin production, and glomerular immune deposits.
Moreover, diabetic Fcg receptor–deficient mice had less mesangial matrix expansion, inflammatory cell
infiltration, and collagen and a-smooth muscle actin content in their kidneys. Accordingly, expression of
genes involved in leukocyte infiltration, fibrosis, and oxidative stress was significantly reduced in diabetic
kidneys and in mesangial cells cultured from Fcg receptor–deficient mice. In summary, preventing the
activation of Fcg receptors alleviates renal hypertrophy, inflammation, and fibrosis in hypercholesterolemic
mice with diabetes, suggesting that modulating Fcg receptor signaling may be renoprotective in
diabetic nephropathy
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