Interference of cyclosporine on glucose metabolism: Potential role in chronic transplantation kidney fibrosis

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.