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

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...

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Bibliographic Details
Published in:Nature reviews. Nephrology 2021-03, Vol.17 (3), p.172-184
Main Authors: Schunk, Stefan J, Floege, Jürgen, Fliser, Danilo, Speer, Thimoteus
Format: Article
Language:English
Subjects:
Animals
Apoptosis
beta Catenin - genetics
beta Catenin - metabolism
Bone diseases
Disease Progression
Fibroblasts
Gene expression
Humans
Kidney diseases
Kinases
Ligands
Nephrology
Phosphorylation
Proteins
Renal Insufficiency, Chronic - genetics
Renal Insufficiency, Chronic - metabolism
Signal Transduction
Wnt Signaling Pathway - genetics
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Summary: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.
ISSN:1759-5061
1759-507X
DOI:10.1038/s41581-020-00343-w