Open Access

Rab7‑mediated autophagy regulates phenotypic transformation and behavior of smooth muscle cells via the Ras/Raf/MEK/ERK signaling pathway in human aortic dissection

  • Authors:
    • Keshuai He
    • Haoliang Sun
    • Junjie Zhang
    • Rui Zheng
    • Jiaxi Gu
    • Ming Luo
    • Yongfeng Shao
  • View Affiliations

  • Published online on: February 14, 2019     https://doi.org/10.3892/mmr.2019.9955
  • Pages: 3105-3113
  • Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Autophagy regulates the metabolism, survival and function of numerous types of cell, including cells that comprise the cardiovascular system. The dysfunction of autophagy has been demonstrated in atherosclerosis, restenotic lesions and hypertensive vessels. As a member of the Ras GTPase superfamily, Rab7 serves a significant role in the regulation of autophagy. The present study evaluated how Rab7 affects the proliferation and invasion, and phenotypic transformations of aortic dissection (AD) smooth muscle cells (SMCs) via autophagy. Rab7 was overexpressed in AD tissues and the percentage of synthetic human aortic SMCs (HASMCs) was higher in AD tissues compared with NAD tissues. Downregulation of Rab7 decreased cell growth, reduced the number of invasive cells and decreased the percentage cells in the G1 phase. Autophagy of HASMCs was inhibited following Rab7 knockdown. Inhibition of autophagy with 3‑methyladenine or Rab7 knockdown suppressed the phenotypic conversion of contractile to synthetic HASMCs. The action of Rab7 may be mediated by inhibiting the Ras/Raf/mitogen‑activated protein kinase (MAPK) kinase (MEK)/extracellular signal related kinase (ERK) signaling pathway. In conclusion, the results revealed that Rab7‑mediated autophagy regulated the behavior of SMCs and the phenotypic transformations in AD via activation of the Ras/Raf/MEK/ERK signaling pathway. The findings of the present study may improve understanding of the role Rab7 in the molecular etiology of AD and suggests the application of Rab7 as a novel therapeutic target in the treatment of human AD.

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APA
He, K., Sun, H., Zhang, J., Zheng, R., Gu, J., Luo, M., & Shao, Y. (2019). Rab7‑mediated autophagy regulates phenotypic transformation and behavior of smooth muscle cells via the Ras/Raf/MEK/ERK signaling pathway in human aortic dissection. Molecular Medicine Reports, 19, 3105-3113. https://doi.org/10.3892/mmr.2019.9955
MLA
He, K., Sun, H., Zhang, J., Zheng, R., Gu, J., Luo, M., Shao, Y."Rab7‑mediated autophagy regulates phenotypic transformation and behavior of smooth muscle cells via the Ras/Raf/MEK/ERK signaling pathway in human aortic dissection". Molecular Medicine Reports 19.4 (2019): 3105-3113.
Chicago
He, K., Sun, H., Zhang, J., Zheng, R., Gu, J., Luo, M., Shao, Y."Rab7‑mediated autophagy regulates phenotypic transformation and behavior of smooth muscle cells via the Ras/Raf/MEK/ERK signaling pathway in human aortic dissection". Molecular Medicine Reports 19, no. 4 (2019): 3105-3113. https://doi.org/10.3892/mmr.2019.9955