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. Author manuscript; available in PMC: 2021 Mar 1.
Published in final edited form as: Semin Nephrol. 2020 Mar;40(2):126–137. doi: 10.1016/j.semnephrol.2020.01.004

Table 2.

Pharmacologic and genetic mediators of Wnt/β-catenin signaling in chronic kidney disease.

Pharmacologic Mechanism Effect Ref
ICG-001 Competitively binds CBP to prevent β-catenin/CBP binding to TCF Reduced fibrosis in models of IRI, UUO, and in vitro models of CKD 52, 65
DKK-1 Binds to LRP5/6 to prevent dimerization with Frizzled and Wnt binding Reduced fibrosis and pericyte activation in UUO models of CKD 25, 74
Klotho Binds to and sequesters Wnt ligands Reduced fibrosis in UUO models of CKD 83
XAV939 Stabilizes Axin to activate destruction complex and stimulate β-catenin degradation Reduced myofibroblast activation in vitro models of CKD 69, 84
sFRP4 Binds Wnt and Frizzled to disrupt signaling functions Reduced fibrosis in UUO models of CKD 69
C59 Binds Porcupine to prevent acylation and secretion of all Wnts Reduced fibrosis in UUO models of CKD 67
Pyrvinium Inhibits axin degradation, which stimulates p-catenin degradation Reduced fibrosis and myofibroblast markers in Ang II injury in vitro 85
Genetic Mechanism Effect Ref
SLC34a1-Cre Wnt1 Overexpression Inducible and sustained Wnt1 production only in proximal tubular epithelium Caused interstitial fibrosis by activation of myofibroblasts without induction by injury 69
Ksp-Cre β-catenin Stabilization β-catenin stabilized (i.e. activated) in tubular epithelium by removing phosphorylation sites that target b-catenin for degradation Caused increased inflammatory infiltration in protein overload injury model 73
Wnt9a Overexpression Overexpression of Wnt9a by delivery of DNA expression plasmids Increased tubular cell senescence and worsened fibrosis in IRI model of CKD 70
Ksp-Cre Wntless Deletion Wntless ablated in tubular epithelium, preventing secretion of Wnts Reduced fibrosis and fibroblast activation in UUO and UIRI models of CKD 71
Gli1-Cre β-catenin Stabilization β-catenin stabilized (i.e. activated) selectively in Gli1+ fibroblasts Activation of myofibroblasts in uninjured kidney 27

Both the pharmacologic and genetic approaches to modulate Wnt/β-catenin signaling in chronic kidney disease are listed as well as mechanism of action, effect on renal injury, and relevant reference. Abbreviations: CBP, cAMP response element-binding (CREB) binding protein; IRI, ischemia-reperfusion injury; UUO, unilateral ureteric obstruction; CKD, chronic kidney disease; DKK-1, Dickkopf-1; LRP5/6, low density lipoprotein (LDL) receptor related protein 5/6; sFRP4, secreted Frizzled-related protein 4; Ang II, angiotensin II; SLC34a1, solute carrier family 34 member 1; Ksp, kidney-specific cadherin.