Table 1.
Pharmacologic | Mechanism | Effect | Ref |
DKK-2 | Binds to LRP5/6 to enhance binding of Wnt and pathway activation | Reduced number of apoptotic tubular epithelial cells in the IRI model of AKI | 12 |
Lithium | nhibits GSK3β activity, preventing β-catenin degradation | Improved renal morphology, especially in proximal tubules, in cisplatin and IRI models of AKI | 35 |
TDZD-8 | Specifically inhibits GSK3β activity, preventing β-catenin degradation | Reduced tubular epithelial cell damage and death in the IRI model of AKI | 39 |
Genetic | Mechanism | Effect | Ref |
γ-GT-Cre GSK3β Deletion | GSK3β ablated specifically in proximal tubular epithelium | Reduced apoptosis and mortality in toxin-induced and IRI models of AKI | 34 |
Ksp-Cre β-catenin Deletion | β-catenin selectively deleted in tubular epithelium | More severe injury and worse mortality in IRI and folic acid models of AKI | 36 |
Gli1-Cre β-catenin Deletion | β-catenin selectively deleted in Gli1+fibroblasts | Attenuated inflammation and tubular injury in IRI model of AKI | 56 |
Listed in this table are the various compounds and genetic models used to study the role of Wnt/β-catenin signaling in acute kidney injury. In addition, the mechanism of action, the model of injury and the effect on injury are represented. Abbreviations: DKK2, Dickkopf-2; LRP5/6, low density lipoprotein (LDL) receptor related protein 5/6; IRI, ischemia- reperfusion injury; AKI, acute kidney injury; GSK3-β, glycogen synthase kinase 3-β; TDZD-8, thiadiazolidinone 8; γ-GT, gamma-glutamyl transferase; Ksp, kidney-specific cadherin.