Klotho Suppresses Epithelial-Mesenchymal Transition In Adriamycin Nephropathy

Klotho interacts with various proteins to alter their function. Experiments were performed to assess how klotho protects kidney from its injury. Adriamycin (5 mg/Kg) was injected into rats to induce nephropathy. Human recombinant klotho (K, 30 μg/kg/day), 4‐benzyl‐2‐methyl‐1,2,4‐thiadiazolidine‐3,5‐dione (GSK3β blocker, 0.2mg/kg/day, T) or vehicle (A) was administered. Rats untreated with adriamycin were used as the control (U). Animals were killed 8 weeks later. Renal expressions of Wnt1, GSK3β, TGFβ1, Twist and collagen I were assessed with RT‐PCR against GAPDH. Results were shown in Table. Our data indicate that WNT is involved in the pathogenesis of adriamycin nephropathy. Furthermore, the present findings provided the evidence that the inhibition of WNT contributed to glomerular protective actions of klotho. Finally, our results suggest that klotho suppresses epithelial‐mesenchymal transition by inhibiting TGFβ as well as WNT signaling. Results U A K T Alb/Cr 8±2 316±39* 152±21*# 163±19*# CCr 1.1±0.1 0.9±0.1 1.0±0.1 1.0±0.1 Wnt1 0.2±0.1 3.6±0.3* 2.3±0.3*# 2.5±0.4*# GSK3β 0.1±0.1 0.8±0.2* 0.4±0.1*# 0.4±0.1*# TGFβ1 1.2±0.2* 0.2±0.1 0.7±0.1*# 0.6±0.2:# Twist 0.1±0.1 1.3±0.2* 0.6±0.1*# 1.1±0.2*$ Collagen I 0.3±0.2 2.3±0.4* 0.7±0.2*# 1.4±0.3*#$ Alb/Cr: Albuminuria(mg)/Creatinine(g), CCr: creatinine clearance (ml/min/g.kidney.wt). *: p<0.05 vs U, #: P<0.05 vs A, $: p<0.05 vs K. Grant Funding Source : Japanese Ministry of Education and Culture (25461229)