Figure 2.

Notch signaling in the adult kidney. Notch signaling is active during nephrogenesis, and the signaling is attenuated after birth in the normal kidney. Reactivation of sustained Notch signaling in the adult kidney either due to genetic activation of Notch signaling or triggered by injury promotes pathological states. Ectopic expression of Notch in mature podocytes results in glomerular dysfunction. The proximal tubules are highly susceptible to injury, and following injury, Jag1 expression increases to activate Notch signaling. Continued high (chronic) Notch signaling leads to fibrosis. This progression can be slowed by blocking Notch signaling either by Gamma secretase inhibitors (GSIs) or by genetic ablation of Notch signaling (PEPCK^CRE; RBPj^f/f). However, a transient increase in Notch after injury maybe beneficial as it initiates the repair process mediated by Sox9+ epithelial cells. In the collecting duct, Notch signaling is required to maintain principal cells (green) in their selected fate. Either increase or decrease of Notch signaling perturbs the ratio of principal cells to intercalated cells seen in normal kidney. Diets such as low potassium or drugs such as lithium also increase intercalated cell numbers at the expense of principal cells, and possibly do so by altering Notch signaling activity.