Journal du diabète clinique

Abstrait

Hippo-YAP is a Potential Target for Treatment of Diabetic Kidney Injury

Jianchun Chen* and Raymond C. Harris*

YAP is a critical downstream effector of the Hippo Signalling Pathway. With activation of the hippo pathway in response to different extracellular cues, YAP is phosphorylated at specific serine/threonine residues by LATS or other kinases, leading to cytoplasmic sequestration, followed by proteasome-mediated degradation. Dephosphorylation and nuclear localization of YAP mediates regulation of multiple transcriptional factors. Aberrant YAP activation caused by mutation of the upstream regulators of the hippo pathway or interaction with other signaling pathways correlates with tumorigenesis and therapeutic resistance in many cancers. Increasing studies have shown that YAP plays important roles in controlling kidney development and function. Recent studies by us and others have indicated that aberrant activation of YAP in kidney cells may contribute to development and progression of diabetic nephropathy. Therefore, targeting the hippo-YAP signaling axis in kidney may be a promising strategy to delay or cure progression of diabetic kidney injury.