Involvement of Notch1 and ALK4/5 Signaling Pathways in Renal Tubular Cell Death: Their Application to Clarification of Cadmium Toxicity

Renal tubular cell death is caused by various extracellular stresses including toxic amounts of cadmium, an occupational and environmental pollutant metal, and is responsible for renal dysfunction. While cadmium exposure disrupts many intracellular signaling pathways, the molecular mechanism underlying cadmium-induced renal tubular cell death has not yet been fully elucidated. We have recently identified two important intracellular signaling pathways that promote cadmium-induced renal tubular cell death: the Notch1 signaling and activin receptor-like kinase (ALK) 4/5 signaling (also known as the activin-transforming growth factor β receptor pathways). In this review paper, we introduce our previous experimental findings, focusing on Notch1 and ALK4/5 signaling pathways, which may uncover the molecular mechanisms involved in cadmium-induced renal tubular cell death.