AMPK/TSC2/mTOR pathway regulates replicative senescence of human vascular smooth muscle cells

  • Authors:
    • Jun‑Kun Zhan
    • Yan‑Jiao Wang
    • Shuang Li
    • Yi Wang
    • Pan Tan
    • Je‑Yu He
    • Yi‑Yin Chen
    • Hui‑Qian Deng
    • Wu Huang
    • Xiao Lin
    • You‑Shuo Liu
  • View Affiliations

  • Published online on: September 19, 2018     https://doi.org/10.3892/etm.2018.6767
  • Pages: 4853-4858
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Abstract

Age‑associated diseases, including vascular diseases, are on the rise with the increase in the aging population. However, the mechanisms of aging and age‑associated vascular dysfunction remain to be fully elucidated. Replicative senescence of vascular smooth muscle cells (VSMCs) contributes to aging as well as age‑associated vascular diseases. Rapamycin may delay aging‑associated diseases via inhibition of the mammalian target of rapamycin (mTOR), but its role in VSMC aging has remained elusive. The present study investigated the involvement of mTOR signaling in replicative senescence of VSMCs. Replicative senescence was induced in human VSMCs by extended passages and identified by assessing the cell morphology, senescence‑associated β‑galactosidase activity, and p53 and p21 protein expression. Protein expression and phosphorylation were determined by western blot analysis. Significant senescence of VSMCs was observed in cells subjected to extended passaging (until passage 15). Significant decreases in adenosine monophosphate‑activated protein kinase (AMPK)/tuberous sclerosis complex 2 (TSC2) phosphorylation, but significant increases in mTOR/ribosomal protein S6 kinase 1 (S6K1) phosphorylation, were observed in cells with replicative senescence compared with those in young cells. Pre‑treatment of VSMCs with AMPK activator and mTOR inhibitor delayed replicative senescence and reversed changes in AMPKα, TSC2, mTOR and S6K1 phosphorylation in senescent VSMCs. The AMPK/TSC2/mTOR/S6K1 signaling axis was found to have an important role in regulating replicative senescence of human VSMCs.
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December-2018
Volume 16 Issue 6

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Zhan JK, Wang YJ, Li S, Wang Y, Tan P, He JY, Chen YY, Deng HQ, Huang W, Lin X, Lin X, et al: AMPK/TSC2/mTOR pathway regulates replicative senescence of human vascular smooth muscle cells. Exp Ther Med 16: 4853-4858, 2018.
APA
Zhan, J., Wang, Y., Li, S., Wang, Y., Tan, P., He, J. ... Liu, Y. (2018). AMPK/TSC2/mTOR pathway regulates replicative senescence of human vascular smooth muscle cells. Experimental and Therapeutic Medicine, 16, 4853-4858. https://doi.org/10.3892/etm.2018.6767
MLA
Zhan, J., Wang, Y., Li, S., Wang, Y., Tan, P., He, J., Chen, Y., Deng, H., Huang, W., Lin, X., Liu, Y."AMPK/TSC2/mTOR pathway regulates replicative senescence of human vascular smooth muscle cells". Experimental and Therapeutic Medicine 16.6 (2018): 4853-4858.
Chicago
Zhan, J., Wang, Y., Li, S., Wang, Y., Tan, P., He, J., Chen, Y., Deng, H., Huang, W., Lin, X., Liu, Y."AMPK/TSC2/mTOR pathway regulates replicative senescence of human vascular smooth muscle cells". Experimental and Therapeutic Medicine 16, no. 6 (2018): 4853-4858. https://doi.org/10.3892/etm.2018.6767