title: Fcγ receptor deficiency attenuates diabetic nephropathy.
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 Fcγ receptors to diabetic renal injury in hyperglycemic, hypercholesterolemic mice. We used streptozotocin to induce diabetes in apolipoprotein E-deficient mice and in mice deficient in both apolipoprotein E and γ-chain, the common subunit of activating Fcγ receptors. After 15 weeks, the mice lacking Fcγ receptors had significantly less albuminuria and renal hypertrophy, despite similar degrees of hyperglycemia and hypercholesterolemia, immunoglobulin production, and glomerular immune deposits. Moreover, diabetic Fcγ receptor-deficient mice had less mesangial matrix expansion, inflammatory cell infiltration, and collagen and α-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 Fcγ receptor-deficient mice. In summary, preventing the activation of Fcγ receptors alleviates renal hypertrophy, inflammation, and fibrosis in hypercholesterolemic mice with diabetes, suggesting that modulating Fcγ receptor signaling may be renoprotective in diabetic nephropathy.
authors.affiliation: Renal and Vascular Inflammation Laboratory, IIS-Fundacion Jimenez Diaz, Autonoma University, Avda Reyes Catolicos, 2 28040 Madrid, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Lopez-Parra
authors.forename: Beñat
authors.initials: B
authors.lastname: Mallavia
authors.forename: Oscar
authors.initials: O
authors.lastname: Lopez-Franco
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Ortiz-Muñoz
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Oguiza
authors.forename: Carlota
authors.initials: C
authors.lastname: Recio
authors.forename: Julia
authors.initials: J
authors.lastname: Blanco
authors.forename: Falk
authors.initials: F
authors.lastname: Nimmerjahn
authors.forename: Jesus
authors.initials: J
authors.lastname: Egido
authors.forename: Carmen
authors.initials: C
authors.lastname: Gomez-Guerrero
mesh_terms: D000199:Actins / Q000378:metabolism; D000419:Albuminuria / Q000453:epidemiology; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D003094:Collagen / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced* / Q000150:complications*; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D004195:Disease Models, Animal; D006984:Hypertrophy / Q000453:epidemiology; D015994:Incidence; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017452:Receptors, IgG / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D013311:Streptozocin / Q000009:adverse effects*
chemical_list: D000199:Actins; D001057:Apolipoproteins E; D017452:Receptors, IgG; C544013:alpha-smooth muscle actin, mouse; D013311:Streptozocin; D003094:Collagen