Modulation of Notch-1 Signaling Alleviates Vascular Endothelial Growth Factor–Mediated Diabetic

OBJECTIVE—Disturbances in podocytes are typically associ-ated with marked proteinuria, a hallmark of diabetic nephropa-thy. This study was conducted to investigate modulation of Notch-1 signaling in high glucose (HG)-stressed human podo-cytes and in a diabetic animal model. RESEARCH DESIGN AND METHODS—Expression of the Notch signaling components was examined in HG-treated podo-cytes, human embryonic kidney cells (HEK293), and kidneys from diabetic animals by RT-qPCR, Western blot analysis, and immunohistochemical staining. The association between the Notch signaling, VEGF expression, and podocyte integrity was evaluated. RESULTS—Notch-1 signaling was significantly activated in HG-cultured human podocytes and HEK293 cells and kidneys from diabetic animals. HG also augmented VEGF expression, decreas