Journal of Jilin University Medicine Edition

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Up-regulation effect of cyclosporine A on level of kidney injury molecule-1 in culture supernatant of human kidney cells and its mechanism

SONG Lian-lian1,2,ZHAO Jun2,YU Jin-yu2,ZHANG Wen-lan2,XUE Li-juan2,FU Yao-wen2   

  1. 1.Department of Pathology,Traditional Chinese Medicine Academy of Sciences of Jilin Province,Changchun 130021,China;2.Urology and Nephrology Center,First Hospital Jilin University,Changchun 130021,China)
  • Received:2014-06-30 Online:2014-11-28 Published:2015-01-18

Abstract:

Abstract:Objective To investigate the mechanism of increasing of the level of kidney injury molecule-1(KIM-1) in culture supernatant of human kidney cells(HKC) induced by cyclosporine A(CsA),and to clarify the relationships between the expression levels of KIM-1 and p38 MAPK pathway and  ERK1/2MAPK pathway in HKC. Methods The HKC at logarithmic growth phase were randomly divided into control group,CsA control group,CsA + p38 kinase inhibitor group,p38 kinase inhibitor group,CsA + ERK1/2 inhibitor group and ERK1/2 kinase inhibitor group. The inhibitory rates of proliferation of HKC in various groups were  detected by MTT assay,and the expression levels of KIM-1 in HKC supernatant in various groups were detected by ELISA;the survival rates,apopototic rates and necrotic rates  of the HKC in various groups  were detected by flow cytometry. Results Compared with control group,the expression level of KIM-1 protein in the supernatant of HKC in CsA control group was significantly increased (P<0.05),and the survival rate was significantly decreased (P<0.05),while the apoptotic rate and the necrotic rate were significantly increased (P<0.05).Compared with control group,the survival rates,the apoptotic rates and the necrosis rates of cells in p38 kinase inhibitor group and ERK1/2 kinase inhibitor group had no significant differences(P>0.05). Compared with CsA control group,the expression levels of KIM-1 protein in CsA + p38 kinase inhibitor group and CsA + ERK1/2 kinase inhibitor group were significantly decreased (P<0.05),and the survival rate was significantly increased (P<0.05),while the apoptotic rate and the necrotic rate were significantly decreased (P<0.05). Conclusion p38 MAPK pathway and ERK1/2MAPK pathway are involved in the process of up-regulation of the KIM-1 level in HKC culture supernatant induced by CsA,and the expression of KIM-1 may become the biochemical marker of clinical monitoring of CsA nephrotoxicity.

Key words: cyclosporine A, kidney injury molecule-1, human kidney cells, p38 MAPK pathway, ERK1/2 MAPK pathway

CLC Number: 

  • R329.28