Abstract P261: GPER is Required for Age-dependent Albuminuria and Glomerulosclerosis: Evidence for its Role in Podocyte Injury and Mesangial Nox1 Regulation

We recently found that the G-protein coupled estrogen receptor (GPER) exerts constitutive effects on cell proliferation and fibrosis in heart failure and arterial hypertension via the NADPH oxidase isoform Nox1 (Sci Signal 2016; 9(452): ra105). Whether GPER affects glomerulosclerosis or podocyte function is unknown. Thus, the present study investigated the effects of GPER in a model of age-dependent spontaneous focal segmental glomerulosclerosis and studied effects of GPER inhibition in mesangial cells and podocytes. Albuminuria and kidney histology were studied in male wild-type (WT) and GPER-deficient (Gper-/-) mice at 4 and 24 months of age. Aged Gper-/-mice were largely protected from albuminuria (albumin/creatinine-ratio, 0.9±0.4 vs. 3.5±1.0, -74 %, p<0.05 vs. WT). Gperdeficiency had no effect at 4 months of age, but largely prevented age-dependent increases in kidney weight (306±11 vs. 554±94 mg), and glomerulosclerosis index (1.3±0.2 vs. 2.9±0.4, p<0.05 vs. WT). All changes were independent of bloo...