Open Access

Sirt1 inhibits HG-induced endothelial injury: Role of Mff-based mitochondrial fission and F‑actin homeostasis-mediated cellular migration

  • Authors:
    • Ruijie Qin
    • Lina Zhang
    • Dong Lin
    • Fei Xiao
    • Lixin Guo
  • View Affiliations

  • Published online on: May 8, 2019     https://doi.org/10.3892/ijmm.2019.4185
  • Pages: 89-102
  • Copyright: © Qin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Although sirtuin 1 (Sirt1) has been found to be involved in diabetic vasculopathy and high glucose (HG)‑mediated endothelial injury, the underlying mechanisms remain to be fully elucidated. The aim of the present study was to investigate the role of Sirt1 in HG‑induced endothelial injury and its potential mechanism. In the present study, it was demonstrated that HG triggers the downregulation of Sirt1 by activating microRNA‑195 in human umbilical vein endothelial cells (HUVECs), as determined by western blot analysis in vivo and in vitro. Furthermore, a lower expression of Sirt1 was correlated with glucose metabolic abnormalities, aortic endothelial dysfunction and endothelial apoptosis as evidenced by western blot analysis and ELISA in mice. By contrast, the loss of Sirt1 evoked mitochondrial fission factor (Mff)‑mediated mitochondrial fission through the c‑Jun N‑terminal kinase (JNK) pathway, which contributes to the apoptosis of HUVECs. In addition, Sirt1 deficiency downregulated the migration of HUVECs through F‑actin dyshomeostasis. Collectively, the results identify Sirt1 as a protective factor, which inhibits the JNK/Mff/mitochondrial fission pathway and sustains F‑actin homeostasis, and has potential implications for novel approaches to diabetic vasculopathy.
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July-2019
Volume 44 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Qin R, Zhang L, Lin D, Xiao F and Guo L: Sirt1 inhibits HG-induced endothelial injury: Role of Mff-based mitochondrial fission and F‑actin homeostasis-mediated cellular migration. Int J Mol Med 44: 89-102, 2019
APA
Qin, R., Zhang, L., Lin, D., Xiao, F., & Guo, L. (2019). Sirt1 inhibits HG-induced endothelial injury: Role of Mff-based mitochondrial fission and F‑actin homeostasis-mediated cellular migration. International Journal of Molecular Medicine, 44, 89-102. https://doi.org/10.3892/ijmm.2019.4185
MLA
Qin, R., Zhang, L., Lin, D., Xiao, F., Guo, L."Sirt1 inhibits HG-induced endothelial injury: Role of Mff-based mitochondrial fission and F‑actin homeostasis-mediated cellular migration". International Journal of Molecular Medicine 44.1 (2019): 89-102.
Chicago
Qin, R., Zhang, L., Lin, D., Xiao, F., Guo, L."Sirt1 inhibits HG-induced endothelial injury: Role of Mff-based mitochondrial fission and F‑actin homeostasis-mediated cellular migration". International Journal of Molecular Medicine 44, no. 1 (2019): 89-102. https://doi.org/10.3892/ijmm.2019.4185