Klotho Protein Affects Rat Osteoblasts To Secrete Fibroblast Growth Factor 23 And Its Mechanism

Objective:To investigate the effect and possible mechanism of Klotho on the expression of fibroblastic growth factor 23(FGF23)secreted by osteoblast-like UMR-106 cells.Methods:UMR-106 cells were cultured in vitro and divided into 5 groups:(1)control group;(2)β-glycerophosphate group;(3)β-glycerophosphate+Klotho group;(4)β-glycerophosphate+LiCl group;(5)β-glycerophosphate+Klotho+LiCl group.The UMR-106 cells were cultured for 72 hours and then the expression of FGF23,P-GSK-3β and GSK-3β protein was measured by Western blotting.The levels of mRNA of FGF23 and c-myc were determined by RT-PCR.Results:1.β-glycerophosphate induced the increase of expression of FGF23 mRNA and protein.Compared with β-glycerophosphate group,FGF23 mRNA and protein expression was downregulated after treating with Klotho.2.β-glycerophosphate induced the increase of expression of P-GSK-3β/GSK-3β and c-myc mRNA.Compared with β-glycerophosphate group,P-GSK-3β/GSK-3β and c-myc mRNA were downregulated after treating with Klotho.3.The expression of FGF23,P-GSK-3β/GSK-3β and c-myc mRNA were upregulated when treated with LiCl.Conclusions:Klotho can downregulate the level of FGF23 induced by P-glycerophosphate secreted by osteoblast-like UMR-106 cells.The possible mechanism may be partially through the inhibition of Wnt/β-catenin signal pathway.Objective: To evaluate the long-term outcomes of patients with cardiac surgery associated-acute kidney injury(CSA-AKI).Methods: Cardiac surgery patients hospitalized in the First Affiliated Hospital of Nanjing Medical University from January 2012 to December 2013 were enrolled in this study.The patients were divided into the AKI and non-AKI groups according to whether developing CSA-AKI and followed up for average 3 years.We recorded the long-term survival rate and the incidence of chronic kidney disease(eGFR<60ml·min-1·1.73m-2)and analyzed the related risk factors.Results: Among all the patients(n=1363),457(33.5%)developed CSA-AKI.The3-year survival rate of the AKI was lower than that of the non-AKI group(88.8% vs 97.2%;P<0.001).CSA-AKI increased the risk of mortality with the hazard ratio of 2.62(95%CI=1.53-4.50).Cox regression analysis showed that AKI was an independent risk factor of mortality adjusted of other factors.The incidence of CKD stages 3-5 in the AKI group was higher than that of the non-AKI(9.9% vs 2.3%;P<0.001).AKI increased the risk of CKD stages 3-5 with the hazard ratio of 3.10(95%CI=1.75-5.48).Cox regression analysis showed that AKI was an independent risk factor of CKD stages 3-5 adjusted of other factors.In addition,elder age and lower baseline eGFR were also associated with the risk of CKD stages 3-5.Conclusions: CSA-AKI increased the risk of 3-year mortality and incidence of CKD stages 3-5.More attention should be paid to the prevention and treatment of CSA-AKI,and long time follow-up of the kidney function is needed.