Inhibition of cell death-inducing p53 target 1 through miR-210-3p overexpression attenuates reactive oxygen species and apoptosis in rat adipose-derived stem cells challenged with Angiotensin II

Chin Hu Lai, Parthasarathi Barik, Dennis Jine Yuan Hsieh, Cecilia Husan Day, Tsung Jung Ho, Ray Jade Chen, Wei Wen Kuo, V. Vijaya Padma, Marthandam Asokan Shibu, Chih Yang Huang

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Hypoxic preconditioning is a well-known strategy to improve the survival and therapeutic potential of stem cells against various challenges including hemodynamic and neurohormonal modulations. However, the mechanism involved in hypoxia-induced benefits on stem cells is still ambiguous. In pathological hypertension, the elevation of the neurohormonal mediator Angiotensin II (Ang II) causes the adverse effects to stem cells. In this study, we investigate the effect and mechanism of action of short term hypoxia-inducible miRNA in suppressing the effects of AngII on stem cells. According to the results obtained, Ang II affects the normal cell cycle and triggers apoptosis in rADSCs with a corresponding increase in the expression of cell death-inducing p53 target 1 (CDIP1) protein. However, the short term hypoxia-inducible miRNA-miR-210-3p was found to target CDIP1 and reduce their levels upon the Ang II challenge. CDIP1 induces stress-mediated apoptosis involving the extrinsic apoptosis pathway via Bid/Bax/cleaved caspase3 activation. Administration of mimic miR-210-3p targets CDIP1 mRNA by binding to the 3′ UTR region as confirmed by dual luciferase assay and also reduced Ang II-induced mitochondrial ROS accumulation as analyzed by MitoSOX staining. Moreover, the present study demonstrates the mechanism of miR-210-3p in the regulation of Ang II-induced CDIP1-associated apoptotic pathway in rADSCs.

Original languageEnglish
Pages (from-to)347-354
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume532
Issue number3
DOIs
Publication statusPublished - Nov 12 2020

Keywords

  • Angiotensin II
  • Apoptosis
  • Hypoxia
  • Mesenchymal stem cells
  • microRNA

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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