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Article Open Access

Hypoxia induces endothelial‑mesenchymal transition in pulmonary vascular remodeling

  • Authors:
    • Bo Zhang
    • Wen Niu
    • Hai‑Ying Dong
    • Man‑Ling Liu
    • Ying Luo
    • Zhi‑Chao Li
  • View Affiliations / Copyright

    Affiliations: Department of Pathophysiology, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 270-278
    |
    Published online on: March 22, 2018
       https://doi.org/10.3892/ijmm.2018.3584
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Abstract

It is well established that hypoxia induces epithelial‑mesenchymal transition in vitro and in vivo. However, the role of hypoxia in endothelial‑mesenchymal transition (EndMT), an important process in the pathogenesis of pulmonary hypertension, is not well‑characterized. The present study demonstrated a significant downregulation of the endothelial marker CD31 and its co‑localization with a mesenchymal marker, α‑smooth muscle actin (α‑SMA), in the intimal layer of small pulmonary arteries of rats exposed to chronic hypoxia. These results suggest a possible role of hypoxia in inducing EndMT in vivo. Consistent with these observations, pulmonary microvascular endothelial cells (PMVECs) cultured under hypoxic conditions exhibited a significant decrease in CD31 expression, alongside a marked increase in the expression of α‑SMA and two other mesenchymal markers, collagen (Col) 1A1 and Col3A1. In addition, hypoxia promoted the proliferation and migration of α‑SMA‑expressing mesenchymal‑like cells, but not of PMVECs. Of note, knockdown of hypoxia‑inducible factor 1α (HIF‑1α) effectively inhibited hypoxic induction of α‑SMA, Col1A1 and the transcription factor Twist1, while rescuing hypoxic suppression of CD31; these results suggest that HIF‑1α is essential for hypoxia‑induced EndMT and that it serves as an upstream regulator of Twist1. Mechanistically, HIF‑1α was identified to bind to the promoter of the Twist1 gene, thus activating Twist1 transcription and regulating EndMT. Collectively, the present results indicate that the HIF‑1α/Twist1 pathway has a critical role in mediating the effect of hypoxia‑induced EndMT in pulmonary arterial remodeling.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang B, Niu W, Dong HY, Liu ML, Luo Y and Li ZC: Hypoxia induces endothelial‑mesenchymal transition in pulmonary vascular remodeling. Int J Mol Med 42: 270-278, 2018.
APA
Zhang, B., Niu, W., Dong, H., Liu, M., Luo, Y., & Li, Z. (2018). Hypoxia induces endothelial‑mesenchymal transition in pulmonary vascular remodeling. International Journal of Molecular Medicine, 42, 270-278. https://doi.org/10.3892/ijmm.2018.3584
MLA
Zhang, B., Niu, W., Dong, H., Liu, M., Luo, Y., Li, Z."Hypoxia induces endothelial‑mesenchymal transition in pulmonary vascular remodeling". International Journal of Molecular Medicine 42.1 (2018): 270-278.
Chicago
Zhang, B., Niu, W., Dong, H., Liu, M., Luo, Y., Li, Z."Hypoxia induces endothelial‑mesenchymal transition in pulmonary vascular remodeling". International Journal of Molecular Medicine 42, no. 1 (2018): 270-278. https://doi.org/10.3892/ijmm.2018.3584
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang B, Niu W, Dong HY, Liu ML, Luo Y and Li ZC: Hypoxia induces endothelial‑mesenchymal transition in pulmonary vascular remodeling. Int J Mol Med 42: 270-278, 2018.
APA
Zhang, B., Niu, W., Dong, H., Liu, M., Luo, Y., & Li, Z. (2018). Hypoxia induces endothelial‑mesenchymal transition in pulmonary vascular remodeling. International Journal of Molecular Medicine, 42, 270-278. https://doi.org/10.3892/ijmm.2018.3584
MLA
Zhang, B., Niu, W., Dong, H., Liu, M., Luo, Y., Li, Z."Hypoxia induces endothelial‑mesenchymal transition in pulmonary vascular remodeling". International Journal of Molecular Medicine 42.1 (2018): 270-278.
Chicago
Zhang, B., Niu, W., Dong, H., Liu, M., Luo, Y., Li, Z."Hypoxia induces endothelial‑mesenchymal transition in pulmonary vascular remodeling". International Journal of Molecular Medicine 42, no. 1 (2018): 270-278. https://doi.org/10.3892/ijmm.2018.3584
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