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

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.

Simvastatin preparations promote PDGF‐BB secretion to repair LPS‐induced endothelial injury through the PDGFRβ/PI3K/Akt/IQGAP1 signalling pathway

“…It is important to identify the upstream regulatory molecules associated with IQGAP1. According to some studies, the PI3K/Akt pathway is not only a crucial regulatory molecule for various cellular functions, but also important in transduction signalling underlying endothelial barrier function during sepsis . In the present study, we found that SV/SV‐NPs activated the PI3K/Akt pathway and promoted Akt phosphorylation, which was inhibited by LPS.…”

“…According to some studies, the PI3K/Akt pathway is not only a crucial regulatory molecule for various cellular functions, but also important in transduction signalling underlying endothelial barrier function during sepsis. [50][51][52][53] In the present study, we found that SV/SV-NPs activated the PI3K/Akt pathway and promoted Akt phosphorylation, which was inhibited by LPS. We then used the PI3K inhibitor LY294002 to determine whether the PI3K/Akt pathway had a mediating function in SV/SV-NPs-induced barrier protection.…”

Study of salivary and serum vaspin and total antioxidants in anorexia nervosa

“…The recent findings that provide evidence of a causal link between vaspin and anti-inflammatory effect were published by Qi et al in 2017 [56]. These studies have confirmed that the use of vaspin in cell culture of human pulmonary microvascular endothelial cells (HPMECs) and stimulated lipopolysaccharide (LPS) exerts an inhibitory effect on both levels of proinflammatory interleukins (IL-6, IL-10) and tumor necrosis factor (TNF-α) as well as activation of nuclear factor-κB (NF-κB) (a pleiotropic factor which stimulates proinflammatory action) [56].…”

“…Collectively, the above investigations have suggested that VASP has a potential role as an anti-inflammatory, anti-apoptotic, and antioxidant biomarker of chronic periodontitis and can be altered after non-surgical treatment in the oral cavity [17,56].…”

“…The mechanism of action of VASP is related, among others, to inhibiting the formation of free radicals under the influence of LPS (research on HPMECs) [56] or methylglyoxal research on vascular smooth muscle cells [58].…”