Korean J Nephrol.  2000 Nov;19(6):1024-1032.

The Effects of Cyclosporine on the Generation of ROS and Extracellular Matrix Accumulation in Cultured Human Mesangial Cells

• Chae HK
• Lee SJ
• Kim HJ
• Kong G
• Kahng KW
• Kang CM

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.

Keyword

ROS(reactive oxygen species); Cyclosporine; Matrix; MMP(matrix metalloproteinase)

MeSH Terms

Cell Proliferation
Cell Survival
Collagen
Cyclosporine*
Extracellular Matrix*
Fibrosis
Gelatin
Humans*
Matrix Metalloproteinase 14
Mesangial Cells*
Oxygen
RNA, Messenger
Tissue Inhibitor of Metalloproteinase-2
Collagen
Cyclosporine
Gelatin
Matrix Metalloproteinase 14
Oxygen
RNA, Messenger
Tissue Inhibitor of Metalloproteinase-2