Table 1.
Regulation and function of Wnt signaling in kidney injury repair and diseases
| AKI | ||||
|---|---|---|---|---|
| Models | Species | Major finding | Role | Ref. |
| IRI | Rat | Wnt4 is induced after AKI and promotes cell cycle progression of renal tubular cells in vitro | Protective | 62 |
| IRI | Mouse | Macrophage-derived Wnt7b promote tubular repair and regeneration | Protective | 25 |
| IRI | Mouse | Tubule-specific ablation of β-catenin aggravates kidney injury | Protective | 24 |
| Folic acid | Mouse | Tubule-specific ablation of β-catenin aggravates kidney injury | Protective | 24 |
| IRI | Rat | Wnt agonist reduces tissue damage and improves renal function | Protective | 64 |
| AKI-to-CKD | ||||
| IRI | Mouse | Transient activation of Wnt/β-catenin is associated with AKI recovery | Transient: protective | 32 |
| Sustained activation of Wnt/β-catenin accelerates AKI-to-CKD progression | Sustained: detrimental | |||
| CKD | ||||
| UUO | Mouse | sFRP4↓, β-catenin↑, sFRP4 inhibits fibrosis | Detrimental | 28 |
| Multiple Wnts↑, β-catenin↑, DKK1 inhibits fibrosis | Detrimental | 26 | ||
| Disruption of β-catenin/CBP by small molecule inhibitor ICG-001 ameliorates fibrosis | Detrimental | 30 | ||
| Klotho antagonizes Wnt and inhibits fibrosis↓ | Detrimental | 48, 126 | ||
| ADR-induced nephropathy | Mouse | Wnts↑, β-catenin↑, podocyte-specific deletion of β-catenin and DKK1 inhibits proteinuria | Detrimental | 27, 127 |
| Sequestration of β-catenin by VDR, reduces proteinuria and fibrosis | Detrimental | 29 | ||
| Antagonism of Wnt/β-catenin by Klotho reduces proteinuria and fibrosis | Detrimental | 48 | ||
| Small molecule inhibitor ICG-001 ameliorates established proteinuria and fibrosis | Detrimental | 77 | ||
| Ang II-induced nephropathy | Mouse | Wnt1↑, β-catenin↑, DKK1 reduces proteinuria | Detrimental | 71 |
| Remnant kidney after 5/6NX | Mouse | Klotho↓, β-catenin↑, antagonism of Wnt by Klotho ameliorates injury, hypertension and fibrosis | Detrimental | 68 |
| Diabetic nephropathy | Akita mice | Multiple Wnts↑,β-catenin↑, anti-LRP6 ameliorates proteinuria and fibrosis | Detrimental | 69 |
| db/db mouse | Multiple Wnts↑, β-catenin↑ | Detrimental | 69 | |
| STZ-diabetic rats | Multiple Wnts↑, β-catenin↑ | Detrimental | 69 | |
| Human | Wnt1↑, β-catenin↑ | Detrimental | 27 | |
| HIV- associated nephropathy | Mouse | Wnt↑, β-catenin↑, DKK1 ameliorates proteinuria and podocytopathy | Detrimental | 72 |
| Human | Wnt↑, β-catenin↑, | Detrimental | 72 | |
| TGF-β1- induced nephropathy | Mouse | TGF-β1 induces Wnt1 in vivo, DKK1 reduces proteinuria | Detrimental | 128 |
| Genetic model | Mouse | Podocyte-specific activation of β-catenin induces proteinuria | Detrimental | 75 |
| Fibroblast-specific activation of β-catenin induces fibrosis | Detrimental | 31 | ||
| Polycystic kidney disease | Mouse | Dysregulated β-catenin, sFRP4, Wnt9b, PCP | Detrimental | 74, 87, 88 |
| IgA nephropathy | Human | β-catenin↑, Inversin↓ | Detrimental | 78 |
| FSGS | Human | Wnt1↑, β-catenin↑ | Detrimental | 27 |
| Lupus nephritis | Human | β-catenin↑, plasma DKK1↑ | Detrimental | 82 |
Abbreviations: IRI, ischemia reperfusion injury; UUO, unilateral ureteral obstruction; ADR, adriamycin; Ang II, angiotensin II; DKK1,Dickkopf 1; LRP-6, low density lipoprotein-related protein 6; STZ, streptozotocin; sFRP4, secreted Frizzled-related protein-4; PCP, planar cell polarity pathway; FSGS, Focal segmental glomerulosclerosis.