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Review
. 2021 Mar;17(3):172-184.
doi: 10.1038/s41581-020-00343-w. Epub 2020 Sep 28.

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

Stefan J Schunk  1 , Jürgen Floege  2 , Danilo Fliser  1 , Thimoteus Speer  3
Affiliations
Review

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

Stefan J Schunk et al. Nat Rev Nephrol. 2021 Mar.

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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