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

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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.

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Acknowledgements

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

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Authors and Affiliations

  1. Department of Child Health Care, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, 410008, Hunan, China

    Qun Huang

  2. Department of Hypertension and Vascular Disease, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China

    Zhen Yang

  3. Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Xiangya Road 87#, Changsha, 410008, Hunan, China

    Ji-Peng Zhou

  4. Department of Geriatric Medicine, Xiangya Hospital, Central South University, Xiangya Road 87#, Changsha, 410008, Hunan, China

    Ying Luo

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  1. Qun Huang
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  2. Zhen Yang
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Correspondence to Ji-Peng Zhou or Ying Luo.

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The authors declare no conflicts of interest.

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Ji-Peng Zhou and Ying Luo have contributed equally to this work.

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Huang, Q., Yang, Z., Zhou, JP. et al. HMGB1 induces endothelial progenitor cells apoptosis via RAGE-dependent PERK/eIF2α pathway. Mol Cell Biochem 431, 67–74 (2017). https://doi.org/10.1007/s11010-017-2976-2

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  • DOI: https://doi.org/10.1007/s11010-017-2976-2

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