Incubation of glomeruli from non-diabetic BAMBI

1 BAMBI acts as a pseudoreceptor for the TGFβ type I receptor family and negative modulator of TGFβ kinase 2 signaling and BAMBI-/-mice show mild endothelial dysfunction. As diabetic glomerular disease is associated 3 with TGFβ overexpression and microvascular alterations, we examined the effect of diabetes on glomerular 4 BAMBI mRNA levels. In isolated glomeruli from biopsies of patients with diabetic nephropathy and in 5 glomeruli from mice with type 2 DM, BAMBI was downregulated. We then examined the effects of BAMBI 6 deletion on streptozotocin-induced diabetic glomerulopathy in mice. BAMBI-/-mice developed more 7 albuminuria with widening of foot processes than BAMBI +/+ mice along with increased activation of alternative 8 TGFβ pathways such as ERK-1/2 and Smad1/5 in glomeruli and cortex of BAMBI-/-mice. Vegfr2 and Angpt1, 9 genes controlling glomerular endothelial stability, were downmodulated in glomeruli from DM BAMBI-/-mice.