Notch3 deficiency protected UUO mice from tubular damage and cell loss with significantly reduced interstitial collagen deposition.387 Loss of histone deacetylase Sirt6 increased the transcription of Notch1 and Notch4 of podocytes.388 The activation of Notch signaling exacerbated podocyte injury, proteinuria, and glomerulosclerosis in mice with DN and adriamycin-induced nephropathy. This evidence concerns the gene NOTCH1 and glomerulosclerosis.