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Molecular and Cellular Biochemistry

, Volume 431, Issue 1–2, pp 67–74 | Cite as

HMGB1 induces endothelial progenitor cells apoptosis via RAGE-dependent PERK/eIF2α pathway

  • Qun Huang
  • Zhen Yang
  • Ji-Peng ZhouEmail author
  • Ying LuoEmail author
Article

Abstract

Studies have demonstrated that the high-mobility group 1B protein (HMGB1) could regulate endothelial progenitor cell (EPC) homing, but the effect of HMGB1 on EPC apoptosis and associated mechanisms are still unclear. The aim of this study was to investigate the effects of HMGB1 on EPC apoptosis and the possible involvement of the endoplasmic reticulum (ER) stress pathway. EPC apoptosis was determined by flow cytometry. The expressions of PERK, eIF2α, and CHOP were detected by western blotting. Additionally, the effects of PERK shRNA on the biological behaviors of EPCs were assessed. Our results showed that incubation of EPCs with HMGB1 (0.1–1 μg/ml) for 12–48 h induced apoptosis as well as activated ER stress transducers, as assessed by up-regulating PERK protein expression and eIF2α phosphorylation in a dose or time-dependent manner. Moreover, HMGB1-mediated EPC apoptosis and CHOP expression were dramatically suppressed by PERK shRNA or a specific eIF2α inhibitor (salubrinal). Importantly, a blocking antibody specifically targeted against RAGE (anti-RAGE antibody) markedly inhibited HMGB1-induced EPC apoptosis and ER stress marker protein (PERK, eIF2α, and CHOP) expression levels. Our novel findings suggest that HMGB1 triggered EPC apoptosis in a manner of RAGE-mediated activation of the PERK/eIF2α pathway.

Keywords

Endothelial progenitor cell High-mobility group 1B Endoplasmic reticulum stress Apoptosis 

Notes

Acknowledgements

This study was supported by the National Natural Science Foundation of China (No. 31270992 and No. 81670453) and China Postdoctoral Science Foundation (2015M582350).

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of Child Health CareHunan Provincial Maternal and Child Health Care HospitalChangshaChina
  2. 2.Department of Hypertension and Vascular Disease, The First Affiliated HospitalSun Yat-Sen UniversityGuangzhouChina
  3. 3.Department of Cardiovascular Medicine, Xiangya HospitalCentral South UniversityChangshaChina
  4. 4.Department of Geriatric Medicine, Xiangya HospitalCentral South UniversityChangshaChina

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