Vaspin protects against LPS‑induced ARDS by inhibiting inflammation, apoptosis and reactive oxygen species generation in pulmonary endothelial cells via the Akt/GSK‑3β pathway

Qi,Di; Wang,Daoxin; Zhang,Chunrong; Tang,Xumao; He,Jing; Zhao,Yan; Deng,Wang; Deng,Xinyu

doi:10.3892/ijmm.2017.3176

Vaspin protects against LPS‑induced ARDS by inhibiting inflammation, apoptosis and reactive oxygen species generation in pulmonary endothelial cells via the Akt/GSK‑3β pathway

Authors:
- Di Qi
- Daoxin Wang
- Chunrong Zhang
- Xumao Tang
- Jing He
- Yan Zhao
- Wang Deng
- Xinyu Deng
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Affiliations: Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China, Department of Emergency, Yongchuan Affiliated Hospital of Chongqing Medical University, Chongqing 402160, P.R. China
Published online on: October 9, 2017 https://doi.org/10.3892/ijmm.2017.3176
Pages: 1803-1817
Copyright: © Qi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acute respiratory distress syndrome (ARDS) is characterized by uncontrolled extravasation of protein‑rich fluids, which is caused by disruption and dysfunction of the barrier of pulmonary endothelial cells (ECs). Visceral adipose tissue‑derived serine protease inhibitor (vaspin) is a novel adipokine with pleiotropic properties, which has been reported to exert beneficial effects against obesity‑associated systemic vascular diseases; however, its effects on ARDS remain unknown. In the present study, mice were subjected to systemic administration of adenoviral vector expressing vaspin (Ad‑vaspin) to examine its effects on lipopolysaccharide (LPS)‑induced ARDS in vivo. Histological analysis was then conducted, and cytokine [tumor necrosis factor (TNF)‑α, interleukin (IL)‑6 and IL‑10] levels, and intercellular cell adhesion molecule‑1 (ICAM‑1) and adherens junctions (AJs) expression were detected. In addition, human pulmonary microvascular ECs (HPMECs) were treated with recombinant human (rh)‑vaspin to further investigate its molecular basis and underlying mechanism. The mRNA expression levels of inflammatory cytokines (TNF‑α and IL‑6) and endothelial‑specific adhesion markers [vascular cell adhesion molecule‑1 and E‑selectin], activation of nuclear factor‑κB, and cell viability and apoptosis were then examined. Furthermore, the expression of AJs and organization of the cytoskeleton, as well as expression and activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and generation of reactive oxygen species (ROS) were determined. The results indicated that Ad‑vaspin protected against LPS‑induced ARDS by alleviating the pulmonary inflammatory response and pulmonary EC barrier dysfunction in mice, which was accompanied by activation of the protein kinase B (Akt)/glycogen synthase kinase (GSK)‑3β pathway. In addition, pretreatment of HPMECs with rh‑vaspin attenuated inflammation, apoptosis and ROS generation without alterations in AJs and cytoskeletal organization following LPS insult, which was accompanied by activation of the Akt/GSK3β pathway. In conclusion, the present study demonstrated that vaspin protects against LPS‑induced ARDS by reversing EC barrier dysfunction via the suppression of inflammation, apoptosis and ROS production in pulmonary ECs, at least partially via activation of the Akt/GSK3β pathway. These findings provide evidence of a causal link between vaspin and EC dysfunction in ARDS, and suggest a potential therapeutic intervention for patients with ARDS.

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