Rosiglitazone inhibits proliferation of renal proximal tubular cells via down-regulation of ERK and Akt : 신장근위세포에서 ERK와 Akt의 하향조절을 통한 Rosiglitazone의 세포증식억제에 관한 연구

다국어 초록 (Multilingual Abstract)

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 treatment 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 and the cell cycle arrest by rosiglitazone. Reactive oxygen species generation and caspase activation were not involved in the anti-proliferative effect of rosiglitazone.
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 by rosiglitazone may play a protective role in kidney cells by preventing injured cells from progressing in the cell cycle.

목차 (Table of Contents)

• Abstract = 1
• Introduction = 2
• Materials and Methods = 4
• Results = 10
• Discussion = 24
• References = 29
• 국문요약 = 43