Angiotensin II inhibits apoptosis of mouse aortic smooth muscle cells through regulating the circNRG-1/miR-193b-5p/NRG-1 axis

Cell Death Dis. 2019 May 1;10(5):362. doi: 10.1038/s41419-019-1590-5.

Abstract

Angiotensin II (Ang II) is known to promote proliferation of vascular smooth muscle cells (VSMCs) in vascular remodeling, but whether it has an anti-apoptotic effect needs to be explored. Neuregulin-1 (NRG-1) as a member of the epidermal growth factor family was reported to suppress the proliferation of VSMCs by activating ErbB receptors, and therefore we hypothesized that there might be a cross talk between the anti-apoptotic effect of Ang II and the anti-proliferative effect of NRG-1 in VSMCs. The aim of the present study was to observe the expression and role of NRG-1 underlying the inhibitory effect of Ang II on apoptosis of mouse aortic smooth muscle cells (MASMCs). It was found that NRG-1 expression was down-regulated via the circNRG-1/miR-193b-5p-mediated post-transcriptional mechanism in response to Ang II. In addition, NRG-1 overexpression reversed the inhibitory effect of Ang II on apoptosis in MASMCs. Our data may provide a molecular basis for further understanding the mechanism of Ang II in suppressing the apoptosis of MASMCs by decreasing NRG-1 expression at circular RNA and micro RNA levels. The circNRG-1/miR-193b-5p/NRG-1 axis may prove to be a potential target for Ang II to inhibit the apoptosis of VSMCs and lead to vascular remodeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / pharmacology*
  • Animals
  • Aorta / cytology
  • Aorta / drug effects
  • Aorta / metabolism
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Line
  • Cell Proliferation / drug effects
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / metabolism
  • Neuregulin-1 / genetics*
  • Neuregulin-1 / metabolism
  • RNA, Circular / genetics*
  • RNA, Circular / metabolism
  • Signal Transduction

Substances

  • MIRN193 microRNA, mouse
  • MicroRNAs
  • Neuregulin-1
  • RNA, Circular
  • Angiotensin II
  • ErbB Receptors