Rosiglitazone inhibits proliferation of renal proximal tubular cells via down-regulation of ERK and Akt.
Rosiglitazone has been reported to exert the protective effect against acute renal failure in animal models. However, the underlying mechanisms by which it protects the damaged kidney cells are poorly understood. The present study was therefore undertaken to examine the effect of rosiglitazone on cell proliferation and to determine its molecular mechanism in opossum kidney (OK) cells, an established renal proximal tubular cell line. Rosiglitazone treatment inhibited cell proliferation in a dose- and time-dependent manner, and such effects were not associated with induction of cell death. The anti-proliferative effect of rosiglitazone was accompanied by the cell cycle arrest at the G1 phase. Western blot analysis data showed that rosiglitazone caused down-regulation of extracellular signal-regulated kinase (ERK) and Akt pathway. Transfection of constitutively active forms of MEK (an upstream kinase of ERK) and Akt prevented the proliferation inhibition induced by rosiglitazone. Rosiglitazone facilitated the recovery of cells after cisplatin-mediated injury. Taken together, these data suggest that rosiglitazone induces inhibition of cell proliferation through ERK and Akt-dependent cell cycle arrest at the G1 phase. The cell cycle arrest may play a protective role in kidney cells by preventing injured cells from progressing in the cell cycle.
Choi
Im Jeong
IJ
Department of Pediatrics, College of Medicine, Pusan National University, Pusan, 602-739, Korea.
Kim
Su Yung
SY
Kwon
Chae Hwa
CH
Kim
Yong Keun
YK
D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects* / Q000502:physiology*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
D045162:Thiazolidinediones; D000077154:Rosiglitazone; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases