Notch pathway mediates podocyte injury and extracellular matrix synthesis in diabetic nephropathy

Background: It remains elusive that Notch pathway mediates podocyte injury and stimulates accumulation of extracellular matrix (ECM) in diabetic nephropathy (DN). This study is aimed at examining the effect of Notch pathway inhibited by gamma-secretase inhibitor on podocyte injury and ECM synthesis in DN. Methods: We examined the expression of Notch1, Notch intracellular domain 1 (NICD1), nephrin, podocin, transforming growth factor-beta 1 (TGF-beta 1), type IV collagen and laminin in high glucose (HG)-induced podocytes and the kidney of diabetic mice using immunofluorescence, immunohistochemistry, Western blot and real-time PCR. The levels of TGF-beta 1, type IV collagen and laminin were determined in the culture medium of the podocytes by enzyme-linked immunosorbent assay. Results: The Notch1, NICD1, TGF-beta 1, type IV collagen and laminin expression increased and the nephrin and podocin expression decreased in HG-induced podocytes and the kidney of diabetic mice. Inhibition of Notch pathway increased nephrin and podocin expression, decreased TGF-beta 1 level and prevented type IV collagen and laminin expression. Conclusions: These findings indicate that Notch pathway mediates podocyte injury and ECM synthesis in DN.