The Role of Notch3 Signaling in Kidney Disease

Notch receptors are transmembrane proteins that are members of the epidermal growth factor-like family. These receptors are widely expressed on the cell surface and are highly conserved. Binding to ligands on adjacent cells results in cleavage of these receptors, and their intracellular domains translocate into the nucleus, where target gene transcription is initiated. In the mammalian kidney, Notch receptors are activated during nephrogenesis and become silenced in the normal kidney after birth. Reactivation of Notch signaling in the adult kidney could be due to the genetic activation of Notch signaling or kidney injury. Notch3 is a mammalian heterodimeric transmembrane receptor in the Notch gene family. Notch3 activation is significantly increased in various glomerular diseases, renal tubulointerstitial diseases, glomerular sclerosis, and renal fibrosis and mediates disease occurrence and development. Here, we discuss numerous recently published papers describing the role of Notch3 signaling in kidney disease.