The inhibition of insulin-stimulated proliferation of vascular smooth muscle cells by rosiglitazone is mediated by the Akt-mTOR-P70S6K pathway

Sungha Park, Soyeon Lim, Woochul Chang, Heesang Song, Sunju Lee, Byeong Wook Song, Hye Jung Kim, Min Ji Cha, Eunju Choi, Yangsoo Jang, Namsik Chung, Seung Yun Cho, Ki Chul Hwang

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16 Citations (Scopus)

Abstract

Purpose: Thiazolidinediones (TZDs) are known to inhibit the proliferation of vascular smooth muscle cell (VSMC) by increasing the activity of p27Kipl and retinoblastoma protein (RB). However, the upstream signaling mechanisms associated with this pathway have not been elucidated. The Akt-mTOR-P70S6 kinase pathway is the central regulator of cell growth and proliferation, and increases cell proliferation by inhibiting the activities of p27Kipl and retinoblastoma protein (RB). Therefore, we hypothesized in this study that rosiglitazone inhibits VSMC proliferation through the inhibition of the Akt-TOR-P70S6K signaling pathway. Materials and Methods: Rat aortic smooth muscle cells (RAoSMCs) were treated with 10μM of rosiglitazone 24 hours before the addition of insulin as a mitogenic stimulus. Western blot analysis was performed to determine the inhibitory effect of rosiglitazone treatment on the Akt-mTOR-P70S6k signaling pathway. Carotid balloon injury was also performed in Otsuka Long-Evans Tokushima Fatty (OLETF) diabetic rats that were pretreated with 3 mg/kg of rosiglitazone. Results: Western blot analysis demonstrated significant inhibition of activation of p-Akt, p-m-TOR, and p-p70S6K in cells treated with rosiglitazone. The inhibition of the activation of the p-mTOR-p-p70S6K pathway seemed to be mediated by both the upstream PI3K pathway and MEK-ERK complex. Conclusion: The inhibitory effect of rosiglitazone on RAoSMC proliferation in vitro and in vivo is mediated by the inhibition of the Akt-mTOR-P70S6K pathway.

Original languageEnglish
Pages (from-to)592-600
Number of pages9
JournalYonsei medical journal
Volume49
Issue number4
DOIs
Publication statusPublished - 2008 Aug

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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    Park, S., Lim, S., Chang, W., Song, H., Lee, S., Song, B. W., Kim, H. J., Cha, M. J., Choi, E., Jang, Y., Chung, N., Cho, S. Y., & Hwang, K. C. (2008). The inhibition of insulin-stimulated proliferation of vascular smooth muscle cells by rosiglitazone is mediated by the Akt-mTOR-P70S6K pathway. Yonsei medical journal, 49(4), 592-600. https://doi.org/10.3349/ymj.2008.49.4.592