WNT–β-catenin signalling—a versatile player in kidney injury and repair

SJ Schunk, J Floege, D Fliser, T Speer - Nature Reviews Nephrology, 2021 - nature.com
SJ Schunk, J Floege, D Fliser, T Speer
Nature Reviews Nephrology, 2021nature.com
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 …
Abstract
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.
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