Table 1.
Effects of Wnt pathway-associated proteins in renal tubular injury excluding polycystic kidney disease
| Effects of Wnt pathway-associated proteins in renal tubular injurya | ||||
|---|---|---|---|---|
| Species | Protein | Injury model | Effect | Reference |
| mouse | Wnt4 | IRI | Expressed in proximal tubules, correlated to cyclin a and d1 | Terada Y et al. JASN 14:1223, 2003 [40] |
| mouse | Wnt4 | FAT injury | Upregulation | Surendran K et al., Kidney Int 65:2212, 2004 [38] |
| mouse | secreted Frizzled-related protein 4 (recombinant) | UUO | Inhibition of β-catenin signaling, reduction of myofibroblasts and fibrosis | Surendran K et al., JASN 16:2373, 2005 [37] |
| mouse | Axin2 | IRI 72/120 h | Activation of canonical Wnt (LacZ indicator) | Lin SL et al., PNAS 107:4194, 2010 [18] |
| mouse | LRP5/LRP6 (LRP5+/−/LRP6+/−) | IRI 72/120 h | Exacerbation of tubular injury in heterozygous deficiency | Lin SL et al., PNAS 107:4194, 2010 [18] |
| mouse | Wnt2, 2b, 4, 7b, 10a | IRI | Upregulation | Lin SL et al., PNAS 107:4194, 2010 [18] |
| mouse | β-catenin/CBP (inhibitor ICG-001) | UUO | Reduction of fibrosis | Hao S et al., JASN 22:1642, 2011 [9] |
| mouse | expression of Klotho (plasmid injection) | UUO (7 days) adriamycin nephropathy (3 weeks) | Reduction of interstitial fibrosis, tubular dilation and fibrosis inhibition by inhibition of β-catenin | Satoh M et al., Am. J. Physiol 303F1641, 2012 [33] |
| mouse | β-catenin−/− | IRI (1 day) FAT injury (2 days) | Exacerbation of tubular injury in heterozygous deficiency | Zhou D et al., Kidney Int 82:537, 2012 [47] |
| mouse | Dapper 3 KO (negative regulator of Wnt) | UUO | Increase in renal fibrosis | Xue H et al., JBC 288:15,006–15,014, 2013 [43] |
| mouse | Wnt (loss of Klotho) | UUO | Increase of fibrosis by Wnt signaling | Zhou L et al., JASN 24:771, 2013 [48] |
| mouse | secreted Frizzled-related protein 1 KO | UUO | Increase in interstitial fibrosis markers and epithelial dedifferentiation by non-canonical Wnt signaling | Matsuyama M et al., JBC 289:31,526–31,533, 2014 [23] |
| mouse | Wnt/β-catenin indicator mice | Acute IRI (30–75–60 min) glycerol-induced acute kidney injury (3 days, 6 days) | Tubular cell regeneration restricted to epithelia with Wnt signaling | Rinkevich Y et al., Cell Rep 4:1270–1283, 2014 [31] |
| rat | Agonist of canonical Wnt/β-catenin 2-amino-4 [3, 4-(methylendioxy) benzylamino] 6- (3-methoxyphenyl) pyrimidine | Bilateral IRI (60 min-24 h) | Decrease of serum creatinine and tubular injury | Kuncewitch M et al., Shock 43:268–275, 2015 [16] |
| mouse | Wnt/β-catenin | Glycerol-induced kidney injury (3 days) | β-catenin/TCF reporter activity in CD24 (progenitor marker) positive injured tubular epithelia | Zhang Z et al., Stem Cells Int. ID391043, 2015 [44] |
| mouse | Porcupine- (Wnt-acyl transferase) Blocker Wnt-C59 | UUO | Blockade of all Wnts, of renal fibrosis, of inflammatory cytokines | Madan B et al., Kidney Int 89:1062, 2016 [21] |
| mouse | Wnt4 | Bilateral IRI (20 min–24 h) | Increase of Wnt4 correlating with tubular injury | Zhao SL Sci Rep 4:32,610, 2016 [45] |
| rat/mouse | PEDF (pigment epithelium-derived factor) | UUO (5 days) | Increase in interstitial inflammation and rise in interstitial fibrosis | He X et al., Kidney Int 91:642–657, 2017 [11] |
| mouse | PRR (pro-renin receptor) | IRI adriamycin angiotensin II infusion | High expression of downstream targets such as fibronectin, plasminogen activator inhibitor 1, and α–smooth muscle actin. Worsening of kidney dysfunction, and worsened renal inflammation and fibrotic lesions | Li Z et al., JASN Mar 7, 2017 [17] |
| mouse | WIs (Wntless, synonym for Evi cargo receptor for Wnts) tubule specific KO | UUO | Reduction of renal fibrosis, myofibroblasts activity | Zohu D et al., JASN Mar 23, 2017 [46] |
IRI ischemia reperfusion injury, FAT injury folic acid tubular injury, UUO unilateral ureteral obstruction
aExcluding polycystic kidney disease