Research Paper Volume 11, Issue 19 pp 8085—8102

Oxidative stress-induced cellular senescence desensitizes cell growth and migration of vascular smooth muscle cells through down-regulation of platelet-derived growth factor receptor-beta

Chun-Hsu Pan1, , Chang-Jui Chen2, , Chun-Ming Shih3, , Ming-Fu Wang4, , Jie-Yu Wang1, , Chieh-Hsi Wu1, ,

  • 1 School of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
  • 2 Department of Pharmacy, Taipei Medical University Hospital, Taipei 11031, Taiwan
  • 3 Division of Cardiology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 11031, Taiwan
  • 4 Department of Food and Nutrition, Providence University, Taichung 433, Taiwan

Received: March 14, 2019       Accepted: September 5, 2019       Published: October 3, 2019
How to Cite

Copyright © 2019 Pan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The relationship between aging and restenosis are unclear. The purposes of this study were to investigate the possible pathological role and mechanism of aging on formation of restenosis. Our data indicated that cell proliferation and migration of the oxidative stress-induced senescent vascular smooth muscle cells were obviously desensitized to stimulation by platelet-derived growth factor (PDGF)-BB, which may have been caused by suppression of promoter activity, transcription, translation, and activation levels of PDGF receptor (PDGFR)-β. The analyzed data obtained from the binding array of transcription factors (TFs) showed that binding levels of eighteen TFs on the PDGFR-β promoter region (-523 to -1) were significantly lower in senescent cells compared to those of non-senescent cells. Among these TFs, the bioinformatics prediction suggested that the putative binding sites of ten TFs were found in this promoter region. Of these, transcriptional levels of seven TFs were markedly reduced in senescent cells. The clinical data showed that the proportion of restenosis was relatively lower in the older group than that in the younger group. Our study results suggested that a PDGFR-β-mediated pathway was suppressed in aging cells, and our clinical data showed that age and the vascular status were slightly negatively correlated in overall participants.


AKT: v-akt murine thymoma viral oncogene homolog 1; Ang II: angiotensin II; CAT: catalase; COUP-TF: nuclear receptor subfamily 2, group F; ERK1/2: extracellular signal-regulated kinase 1/2; FOXD3: forkhead box D3; FOXG1: forkhead box G1; GR/PR: glucocorticoid receptor / progesterone receptor; HIF-1α: hypoxia-inducible factor 1-alpha; HOX4C: homeobox 4C; MEF1: myocyte enhancer factor 1; mTOR: the mechanistic target of rapamycin; NFAT: nuclear factor of activated T-cells; NOS: nitric oxide synthase; NRF1: nuclear respiratory factor 1; OCT4: POU class 5 homeobox 1; Pbx1: pre-B cell leukemia transcription factor-1; PDGF-BB: platelet-derived growth factor-BB; PDGFR-β: platelet-derived growth factor receptor-beta; PPAR: peroxisome proliferator-activated receptor; PXR: pregnane X receptor; ROS: reactive oxygen species; SA-β-gal: senescence-associated beta-galactosidase; SATB1: special AT-rich sequence binding protein 1; SMUC: snail-related transcription factor Smuc; SOD: superoxide dismutase; STAT5: signal transducer and activator of transcription 5; TFIID: TATA box binding protein; TFs: transcription factors; TCF/LEF: runt-related transcription factor 2; USF-1: upstream transcription factor 1; VSMCs: vascular smooth muscle cells.