Up-regulation effect of cyclosporine A on level of kidney inj ury molecule-1 in culture supernatant of human kidney cells and its mechanism / 吉林大学学报(医学版)

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 (P0.05).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.