The Effects of Cyclosporine on the Generation of ROS and Extracellular Matrix Accumulation in Cultured Human Mesangial Cells.
- Author:
Hyun Ki CHAE
1
;
Su Jeen LEE
;
Hyun Jun KIM
;
Gu KONG
;
Kyoung Won KAHNG
;
Chong Myung KANG
Author Information
1. Department of Internal Medicine, College of Medicine, Hanyang University, Seoul, Korea.
- Publication Type:In Vitro ; Original Article
- Keywords:
ROS(reactive oxygen species);
Cyclosporine;
Matrix;
MMP(matrix metalloproteinase)
- MeSH:
Cell Proliferation;
Cell Survival;
Collagen;
Cyclosporine*;
Extracellular Matrix*;
Fibrosis;
Gelatin;
Humans*;
Matrix Metalloproteinase 14;
Mesangial Cells*;
Oxygen;
RNA, Messenger;
Tissue Inhibitor of Metalloproteinase-2
- From:Korean Journal of Nephrology
2000;19(6):1024-1032
- CountryRepublic of Korea
- Language:Korean
-
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 10microgram/ mL) and also with cyclosporine(5microgram/mL) plus N- acetylcysteine(1mM). 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.
