Interference of cyclosporine on glucose metabolism: potential role in chronic transplantation kidney fibrosis.
Transplantation Proceedings(2006)
摘要
Objectives. To explore the fibrosis induction effects of cyclosporine (CsA) on renal tubular epithelial cells, as well as the potential mechanisms of Cs.A-mediated alterations of glucose metabolism in chronic allograft nephropathy (CAN). Methods. The rat renal tubular epithelial cell line NRK-52E cells were cultured in medium with 50 mmol/L of D-glucose for 7, 14, or 28 days. The expression of TGF-beta 1, CTGF, Smad3, and Smad7, which are involved in the fibrosis signal pathway, was detected by immunofluorescence and reverse-transcriptase polymerase chain reaction. Meanwhile, cells were cultured in various concentration of CsA in glucose-free medium for 24 hours followed by the addition of D-[3-H-3]-glucose for 30 minutes; glucose uptake was detected by examining the radiation intensity. Results. The expression of TGF-beta 1, Smad3, Smad7, and CTGF of NRK-52E cells were up-regulated significantly (P <.05) after culture with 50 mmoM glucose for 7 days compared with those in 25 mmol/L glucose. At 14 and 28 days, TGF-beta 1 was slightly decreased compared with 7 days, but CrGF, Smad3, and Smad7 increased robustly (P <.05). C&A significantly stimulated glucose uptake at various concentrations, with an absorption peak at 60 minutes that decreased at 75 minutes. Furthermore, CsA may have dose-dependent effects on glucose uptake. Conclusion. High glucose concentrations may play an important role in the NRK-52E cell fibrosis during the CAN process due to an interference of CsA on glucose metabolism.
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关键词
glucose metabolism
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