Author:
Rashmi Priyanka,Silva Andrea Alice,Sigdel Tara,Damm Izabella,Gouvêa Ana Luisa Figueira,Koliwad Suneil,Walavalkar Vighnesh,Hakroush Samy,Sarwal Minnie M.
Abstract
AbstractFcER1 forms a high affinity multimeric cell-surface receptor for the Fc region of immunoglobulin E (IgE) and controls the activation of mast cells and basophils. Antigen binding and cross-linking of FcER1 associated IgE induces several downstream signaling pathways that result in diverse outcomes. Canonical signaling through IgE-FcER1 has been related to allergic responses, however, recent studies have identified that their function in mast cell and basophils contribute to other pathogenic conditions such as cancer and diabetes. Previous studies have demonstrated that FcER1 protein is upregulated in advanced diabetic kidney disease (DKD) making it a targetable molecule for the treatment of DKD. This study presents evidence that loss of FcER1 signaling reduces proteinuria and renal injury in two pre-clinical mouse models of diabetes. Mice deficient for fcer1 are protected from streptozotocin mediated induction of proteinuria and display reduced fibrosis and mast cell infiltration in kidney. Furthermore, inhibition of FcER1 signaling with an antibody directed against the γ-subunit reduces proteinuria in a spontaneous model of type II diabetes. Our results show significant reduction of proteinuria and tissue damage in pre-clinical DKD models demonstrating the potential of FcER1 inhibitory approaches for developing new therapies in DKD.
Publisher
Cold Spring Harbor Laboratory
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