Dexmedetomidine alleviates pulmonary edema through the epithelial sodium channel (ENaC) via the PI3K/Akt/Nedd4-2 pathway in LPS-induced acute lung injury

Jiang, Yibin; Xia, Mingzhu; Xu, Jing; Huang, Qiang; Dai, Zhongliang; Zhang, Xueping

doi:10.1007/s12026-021-09176-6

Cited by 20 publications

(22 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Li et al (2018) and Sun et al(2019) reported that Dex has a protective effect on LPS or renal ischemiareperfusion induced alveolar epithelial cells and pulmonary microvascular endothelial cells by the activation of α2AR/PI3K /Akt pathway. Our previous studies have shown that Dex reduces pulmonary edema by activating the PI3K/Akt /Nedd4-2 pathway (Jiang et al 2021). In addition, the increased expression of Na,K-ATPase is related to the activation of PI3K/Akt pathway (Bhargava et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine Promotes Alveolar Fluid Clearance by Upregulating Na,K-ATPase Expression in a Rat Model of Acute Lung Injury via α2 AR/PI3K/Akt Pathway

Xia

Huang

Ming-yu

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Our previous studies have shown that Dexmedetomidine (Dex), α2 adrenergic receptor (α2AR) agonist, reduces pulmonary edema in LPS-induced acute lung injury (ALI), but the mechanism is not clear. The purpose of this study is to explore whether Dex promotes AFC by upregulating the expression of Na,K-ATPase in LPS-induced ALI and possible molecular mechanisms. Histology of the lungs was assayed with H-E staining, and the lung injury score was calculated. PaO2, PaO2/FiO2 , the lung index, wet/dry (W/D) ratio of the lung tissues and alveolar fluid clearance(AFC) was measured; The concentrations of TNF-α, IL-1β, IL-6 in bronchoalveolar lavage fluid (BALF) and serum were measured. Myeloperoxidase (MPO) activity in lung tissues were determined. The apoptosis rate of A549 cells and the expression of Bcl-2 and Bax were evaluated. The expression of Na,K-ATPase , p-PI3K and p-Akt in vivo and in vitro were evaluated. Dex significantly alleviated lung tissue injury induced by LPS. Dex treatment reduced the W/D, lung index and MPO activity, increased PaO2, PaO2/FiO2 and AFC in LPS-induced ALI. In addition, Dex reduced the concentrations of TNF-α, IL-β and IL-6 in BALF and serum. Dex reduced the apoptosis rate, up-regulated the expression of Bcl-2 and down-regulated the expression of Bax in LPS-stimulated A549 cells. Furthermore, Dex increased the expression of α1Na,K-ATPase, β1 Na,K-ATPase and p-PI3K , p-Akt in vivo and vitro. However, these effects of Dex were partially reversed by the α2AR inhibitor yohim-bine or PI3K inhibitor LY294002. Collectively, these results suggest that Dex attenuates pulmonary edema by stimulating AFC via upregulating the Na,K-ATPase expressi-on in LPS-induced acute lung injury by modulating the α2AR/PI3K/Akt signaling pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine Promotes Alveolar Fluid Clearance by Upregulating Na,K-ATPase Expression in a Rat Model of Acute Lung Injury via α2 AR/PI3K/Akt Pathway

Xia

Huang

Ming-yu

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, one may notice that the research reports on the PI3K/Akt signaling pathway were controversial in the studies of LPS-induced acute lung injury (ALI). There is still no clear result on whether the activation or inhibition of the PI3K/Akt signaling pathway on the protective effect of ALI [47][48][49][57][58][59]. Readers may find the details about the relationship between PI3K/Akt signaling pathway and ALI in the Additional file.…”

Section: Discussionmentioning

confidence: 99%

Aqueous extract of Platycodon grandiflorus attenuates lipopolysaccharide-induced apoptosis and inflammatory cell infiltration in mouse lungs by inhibiting PI3K/Akt signaling

et al. 2023

View full text Add to dashboard Cite

Background Acute lung injury (ALI), an acute inflammatory lung disease, can cause a rapid inflammatory response in clinic, which endangers the patient's life. The components of platycodon grandiflorum, such as platycodins have a wide range of pharmacological activities such as expectorant, anti-apoptotic, anti-inflammatory, anti-tumor and anti-oxidant properties, and can be used for improving human immunity. Previous studies have shown that aqueous extract of platycodon grandiflorum (PAE) has a certain protective effect on ALI, but the main pharmacodynamic components and the mechanism of action are not clear. Methods The anti-inflammatory properties of PAE were studied using the lipopolysaccharide (LPS)-induced ALI animal model. Hematoxylin and eosin stains were used to assess the degree of acute lung damage. Changes in RNA levels of pro-inflammatory cytokines in the lungs were measured using quantitative RT-qPCR. The potential molecular mechanism of PAE preventing ALI was predicted by lipidomics and network pharmacology. To examine the anti-apoptotic effects of PAE, TdT-mediated dUTP nick-end labelling (TUNEL) was employed to determine apoptosis-related variables. The amounts of critical pathway proteins and apoptosis-related proteins were measured using Western blotting. Results Twenty-six chemical components from the PAE were identified, and their related pathways were obtained by the network pharmacology. Combined with the analysis of network pharmacology and literature, it was found that the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway is related to ALI. The results of lipidomics show that PAE alleviates ALI via regulating lung lipids especially phosphatidylinositol (PI). Finally, the methods of molecular biology were used to verify the mechanism of PAE. It can be found that PAE attenuates the inflammatory response to ALI by inhibiting apoptosis through PI3K/Akt signaling pathway. Conclusion The study revealed that the PAE attenuates lipopolysaccharide-induced apoptosis and inflammatory cell infiltration in mouse lungs by inhibiting PI3K/Akt signaling. Furthermore, our findings provide a novel strategy for the application of PAE as a potential agent for preventing patients with ALI.

show abstract

“…DEX could reduce inflammation and the mortality of sepsis animal models, possibly because it enhanced the activity of the immune system, but the reduced systemic response and the concentration of proinflammatory cytokines (TNF-α, IL-1β, IL-6)(Dardalas et al 2019 ). Previous research pointed out that DEX may exert an anti-inflammatory function in ALI through multiple complex molecular mechanisms, including improving epithelial sodium channel (ENaC) (Jiang et al 2021 ), upregulating tumor necrosis factor-α-induced protein-8-like 2 (TIPE2)(Kong et al 2020 ), and activating the NLRP3 inflammasome in alveolar macrophages (Y. Chen et al 2020b , a ). We established an ALI model induced by CLP, and then DEX was used for treatment.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine alleviates acute lung injury by promoting Tregs differentiation via activation of AMPK/SIRT1 pathway

et al. 2022

View full text Add to dashboard Cite

Objectives To explore the anti-inflammatory effect and the potential mechanism of dexmedetomidine in ARDS/ALI. Materials and Methods C57BL/6 mice and EL-4 cells were used in this research. The ALI model was established by CLP. The level of inflammatory cytokines in the lung and blood, the severity of lung injury, the expression of Foxp3, and the proportion of Tregs were detected before and after dexmedetomidine treatment. The expression of the AMPK/SIRT1 after dexmedetomidine treatment was detected in vivo and in vitro. After blocking the AMPK/SIRT1 pathway or depleting Tregs in vivo, the level of the inflammatory response, tissue injury, and Tregs differentiation were detected again to clarify the effect of dexmedetomidine. Results Dexmedetomidine significantly reduced systemic inflammation and lung injury in CLP mice. Dexmedetomidine enhanced the Foxp3 expression in the lungs and the frequency of Tregs in the spleen. Dexmedetomidine up-regulated the protein expression of p-AMPK and SIRT1 in lungs and EL-4 cells and facilitated the differentiation of naïve CD4 + T cells into Tregs in vitro. Meanwhile, DEX also increased the expression of Helios in Treg cells. Conclusions DEX could improve ARDS/ALI by facilitating the differentiation of Tregs from naïve CD4 + T cells via activating the AMPK/SIRT1 pathway.

show abstract

Dexmedetomidine alleviates pulmonary edema through the epithelial sodium channel (ENaC) via the PI3K/Akt/Nedd4-2 pathway in LPS-induced acute lung injury

Cited by 20 publications

References 43 publications

Dexmedetomidine Promotes Alveolar Fluid Clearance by Upregulating Na,K-ATPase Expression in a Rat Model of Acute Lung Injury via α2 AR/PI3K/Akt Pathway

Dexmedetomidine Promotes Alveolar Fluid Clearance by Upregulating Na,K-ATPase Expression in a Rat Model of Acute Lung Injury via α2 AR/PI3K/Akt Pathway

Aqueous extract of Platycodon grandiflorus attenuates lipopolysaccharide-induced apoptosis and inflammatory cell infiltration in mouse lungs by inhibiting PI3K/Akt signaling

Dexmedetomidine alleviates acute lung injury by promoting Tregs differentiation via activation of AMPK/SIRT1 pathway

Contact Info

Product

Resources

About