WNT-β-catenin signalling - a versatile player in kidney injury and repair.
Stefan J SchunkJürgen FloegeDanilo FliserThimoteus SpeerPublished in: Nature reviews. Nephrology (2020)
The WNT-β-catenin system is an evolutionary conserved signalling pathway that is of particular importance for morphogenesis and cell organization during embryogenesis. The system is usually suppressed in adulthood; however, it can be re-activated in organ injury and regeneration. WNT-deficient mice display severe kidney defects at birth. Transient WNT-β-catenin activation stimulates tissue regeneration after acute kidney injury, whereas sustained (uncontrolled) WNT-β-catenin signalling promotes kidney fibrosis in chronic kidney disease (CKD), podocyte injury and proteinuria, persistent tissue damage during acute kidney injury and cystic kidney diseases. Additionally, WNT-β-catenin signalling is involved in CKD-associated vascular calcification and mineral bone disease. The WNT-β-catenin pathway is tightly regulated, for example, by proteins of the Dickkopf (DKK) family. In particular, DKK3 is released by 'stressed' tubular epithelial cells; DKK3 drives kidney fibrosis and is associated with short-term risk of CKD progression and acute kidney injury. Thus, targeting the WNT-β-catenin pathway might represent a promising therapeutic strategy in kidney injury and associated complications.
Keyphrases
- cell proliferation
- stem cells
- acute kidney injury
- epithelial mesenchymal transition
- chronic kidney disease
- cardiac surgery
- transcription factor
- pregnant women
- oxidative stress
- cell therapy
- genome wide
- gene expression
- single cell
- blood brain barrier
- postmenopausal women
- body composition
- wound healing
- mesenchymal stem cells
- diabetic nephropathy