Figure 8.

Ang II activates the Notch1/Snail signaling, which is responsible for the pathogenesis of proteinuria in diabetic nephropathy. Schematic drawing summarizes the molecular pathway by which Ang II, after binding with angiotensin type 1 receptor (AT₁R), induces increased activation of Notch1. The active Notch1 (ICN1) via the downstream target gene, HES1, increases the expression of Snail and its translocation into the nucleus, leading to nephrin down-regulation. This series of events is responsible for the molecular podocyte lesions and loss of the glomerular permeability in diabetes.