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

Yonsei Medical Journal
Sungha ParkKi-Chul Hwang

Abstract

Thiazolidinediones (TZDs) are known to inhibit the proliferation of vascular smooth muscle cell (VSMC) by increasing the activity of p27Kip1 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 p27Kip1 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. Rat aortic smooth muscle cells (RAoSMCs) were treated with 10microM 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. 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 ...Continue Reading

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Citations

Jul 28, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·Aiko OgawaJason X-J Yuan
Aug 24, 2013·Journal of Pharmacy Practice·Jonathan L RabeyAlice C Ceacareanu
Aug 5, 2016·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Ahmad HanifMohammed A Nayeem
Mar 27, 2021·Frontiers in Pharmacology·Yunyun ZhaoZhongqun Wang

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Methods Mentioned

BETA
protein assay
light microscopy
fluorescence microscopy

Software Mentioned

Photo
MetaMorph
- Image System

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AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.