Korean Journal of Nephrology 2000;19(6):1024-1032.

사람의 혈관간세포에서 Cyclosporine이 반응성 신소종 ( Reactive Oxygen Species )과 세포의 기질 축적에 미치는 영향 (The Effects of Cyclosporine on the Generation of ROS and Extracellular Matrix Accumulation in Cultured Human Mesangial Cells)

채현기(Hyun Gee Chae),이수진(Soo Jin Lee),김현준(Hyun Joon Kim),공구(Goo Kong),강경원(Gyung Won Kang),강종명(Jong Myung Kang)

Abstract

Objective: Treatment with cyclosporine(CsA) for a long-term period may induce renal glomerulosclersosis and interstitial fibrosis. Reactive oxygen species(ROS) seems to be involved in the process of glomerulosclersosis and interstitial fibrosis. We investigated the effect of CsA on the generation of ROS and extracellular matrix accumulation in cultured human mesangial cells. We also studied the relationship between ROS formation and extracellular matrix and the effect of antioxidant on ROS formation and/or extracellular matrix degradation. Methods: Mesangial cells were treated with varying dose of Cyclosporine(0, 2.5, 5, 7.5 and 10 μg/mL) and also with cyclosporine(5μg/mL) plus N-acetylcysteine(lmM). ROS was measured by flow cytometric analysis. mRNA expression of MMP-2, TIMP-2, MT1-MMP and collagen III was assessed by RT-PCR method. MMP-2 activity was measured by gelatin zymography. Results: No significant difference was noted in cell viability with each CsA concentration. CsA inhibited the cell proliferation in a dose dependent manner and induced the expression of ROS. Antioxidant NAC reversed the effect of cyclosporine. CsA had no effect on the mRNA expression of collagen III, MMP-2, TIMP-2, MT1-MMP. However CsA decreased the MMP-2 activity in a dose dependent manner, which was also reversed by NAC. Conclusion: Cyclosporine-induced ROS may be associated with the extracellular matrix accumulation, that is glomerulosclersosis and interstitial fibrosis by inhibiting the cell proliferation and by decreasing the degradation of extracellular matrix. Antioxidant, at least in vitro, may prevent some of the adverse effects of CsA on renal function.