Rac1 mediates HMGB1‑induced hyperpermeability in pulmonary microvascular endothelial cells via MAPK signal transduction

  • Authors:
    • Min Shao
    • Song‑Tao Tang
    • Bao Liu
    • Hua‑Qing Zhu
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  • Published online on: November 6, 2015     https://doi.org/10.3892/mmr.2015.4521
  • Pages: 529-535
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Abstract

The pathology of acute respiratory distress syndrome (ARDS) is closely associated with the failure of alveolar‑capillary barrier integrity and alveolar filling by high protein pulmonary edema, resulting from hyperpermeability. High mobility group box 1 (HMGB1) is a novel late mediator of sepsis, which is specifically involved in endotoxin‑induced acute lung injury and sepsis‑associated lethality. Although the role of HMGB1 in endothelial cell cytoskeletal rearrangement and vascular permeability have been investigated preliminarily, the molecular mechanisms remain to be fully elucidated. As the ras‑related C3 botulinum toxin substrate 1 (Rac1) gene is important role in regulating microvascular barrier maintenance, the present study was designed to determine whether Rac1 is involved in HMGB1‑induced hyperpermeability in pulmonary microvascular endothelial cells (PMVECs). The results of the present study demonstrated that HMGB1 induced dose and time‑dependent decreases in transendothelial electrical resistance (TER). Notably, HMGB1 induced a dose‑dependent increase in the activity and expression levels of Rac1. Using small interfering RNA and an agonist of Rac1, the present study demonstrated that Rac1 was a novel factor mediating the HMGB1‑induced decrease in TER via extracellular signal‑regulated kinase and p38 mitogen‑activated protein kinase (MAPK) activation. These data suggested that Rac1 is involved in HMGB1‑induced hyperpermeability in PMVECs via MAPK signal transduction.
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January-2016
Volume 13 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Shao M, Tang ST, Liu B and Zhu HQ: Rac1 mediates HMGB1‑induced hyperpermeability in pulmonary microvascular endothelial cells via MAPK signal transduction. Mol Med Rep 13: 529-535, 2016
APA
Shao, M., Tang, S., Liu, B., & Zhu, H. (2016). Rac1 mediates HMGB1‑induced hyperpermeability in pulmonary microvascular endothelial cells via MAPK signal transduction. Molecular Medicine Reports, 13, 529-535. https://doi.org/10.3892/mmr.2015.4521
MLA
Shao, M., Tang, S., Liu, B., Zhu, H."Rac1 mediates HMGB1‑induced hyperpermeability in pulmonary microvascular endothelial cells via MAPK signal transduction". Molecular Medicine Reports 13.1 (2016): 529-535.
Chicago
Shao, M., Tang, S., Liu, B., Zhu, H."Rac1 mediates HMGB1‑induced hyperpermeability in pulmonary microvascular endothelial cells via MAPK signal transduction". Molecular Medicine Reports 13, no. 1 (2016): 529-535. https://doi.org/10.3892/mmr.2015.4521