Ouabain Protects Mice Against Lipopolysaccharide-Induced Acute Lung Injury

Wang, Changli; Meng, Yan; Wang, Yuanyuan; Jiang, Zhengyu; Xu, Mengda; Bo, Lulong; Deng, Xiaoming

doi:10.12659/msm.908627

Cited by 17 publications

(15 citation statements)

References 40 publications

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“…12 Many previous studies have been consistent with our findings that MAPK signaling pathways play an important role in the induction of ALI. [13][14][15] Previous analyses based on gene microarray have found differences in circRNAs expression of LPS-induced rat models. 16 However, specific function and pathway analysis, as well as its possible regulatory network, have not been reported.…”

Section: Discussionmentioning

confidence: 99%

Microarray analysis reveals the changes of circular RNA expression and molecular mechanism in acute lung injury mouse model

Yuan

Wang

et al. 2019

J of Cellular Biochemistry

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Acute lung injury (ALI) is a severe disease with sudden onset, rapid progression, poor treatment response, and high mortality. An increasing number of studies had found that circular RNAs (circRNAs) has significant functions in various diseases, while the role of circRNAs in ALI is not yet clear. The purpose of this study was to find circRNAs related to ALI and their mechanism of action. Expression profiles of lung circRNAs and messenger RNAs (mRNAs) were analyzed by microarray in the ALI mice models and healthy controlled mice. Differentially expressed RNAs were identified, function and pathways were analyzed by bioinformatics analysis. Moreover, the results of the microarray were verified by real‐time PCR. We identified 2262 differentially expressed mRNAs and 581 circRNAs between ALI mice and control. Validation of candidate circRNAs by real‐time PCR indicates that the majority of circRNAs identified by microarray are reliable and worthy of further study. ALI induced circRNAs primarily function in the metabolic regulatory process. Moreover, differentially expressed circRNAs were mainly involved in signaling pathways of mitogen‐activated protein kinases, focal adhesion, FoxO, neurotrophin, and Wnt. In addition, a competitive endogenous RNA network was constructed to further interpret the molecular mechanism of ALI. This study observed significantly changed circRNAs profiles in LPS‐induced mouse model and revealed a potential role of circRNAs in ALI.

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Section: Discussionmentioning

confidence: 99%

Microarray analysis reveals the changes of circular RNA expression and molecular mechanism in acute lung injury mouse model

Yuan

Wang

et al. 2019

J of Cellular Biochemistry

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“…Ouabain suppresses the production of IL-6 and TNFα by peripheral blood mononuclear cells that have been activated with lipopolysaccharide (LPS) from E. coli, protecting from LPSinduced lethality (Matsumori et al, 1997). The protective effect of ouabain was further studied in mouse acute lung injuries; ouabain decreased TNFα, IL-1β, and IL-6 production, diminished neutrophil and mononuclear influx, and reduced pulmonary permeability and edema formation (Wang et al, 2018). Furthermore, in a model of airway allergic inflammation, ouabain decreased the levels of IL-13 and IL-4 in bronchoalveolar lavage fluid, cell migration into peribronchiolar and perivascular areas, and mucus production in bronchioles (Galvao et al, 2017).…”

Section: Cgs As Anti-inflammatory Drugsmentioning

confidence: 99%

Na+/K+-ATPase as a Target of Cardiac Glycosides for the Treatment of SARS-CoV-2 Infection

et al. 2021

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), identified for the first time in Wuhan, China, causes coronavirus disease 2019 (COVID-19), which moved from epidemic status to becoming a pandemic. Since its discovery in December 2019, there have been countless cases of mortality and morbidity due to this virus. Several compounds such as chloroquine, hydroxychloroquine, lopinavir-ritonavir, and remdesivir have been tested as potential therapies; however, no effective treatment is currently recommended by regulatory agencies. Some studies on respiratory non-enveloped viruses such as adenoviruses and rhinovirus and some respiratory enveloped viruses including human respiratory syncytial viruses, influenza A, parainfluenza, SARS-CoV, and SARS-CoV-2 have shown the antiviral activity of cardiac glycosides, correlating their effect with Na+/K+-ATPase (NKA) modulation. Cardiac glycosides are secondary metabolites used to treat patients with cardiac insufficiency because they are the most potent inotropic agents. The effects of cardiac glycosides on NKA are dependent on cell type, exposure time, and drug concentration. They may also cause blockage of Na+ and K+ ionic transport or trigger signaling pathways. The antiviral activity of cardiac glycosides is related to cell signaling activation through NKA inhibition. Nuclear factor kappa B (NFκB) seems to be an essential transcription factor for SARS-CoV-2 infection. NFκB inhibition by cardiac glycosides interferes directly with SARS-CoV-2 yield and inflammatory cytokine production. Interestingly, the antiviral effect of cardiac glycosides is associated with tyrosine kinase (Src) activation, and NFκB appears to be regulated by Src. Src is one of the main signaling targets of the NKA α-subunit, modulating other signaling factors that may also impair viral infection. These data suggest that Src-NFκB signaling modulated by NKA plays a crucial role in the inhibition of SARS-CoV-2 infection. Herein, we discuss the antiviral effects of cardiac glycosides on different respiratory viruses, SARS-CoV-2 pathology, cell signaling pathways, and NKA as a possible molecular target for the treatment of COVID-19.

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“…LPS is known to increase intestinal epithelial TJ permeability and plays an important role in mediating intestinal inflammatory responses [ 35 ]. Recently, a protective effect of ouabain against LPS-induced acute lung injury in mice was shown [ 36 ].…”

Section: Resultsmentioning

confidence: 99%

Circulating Ouabain Modulates Expression of Claudins in Rat Intestine and Cerebral Blood Vessels

Markov

Fedorova

Кравцова

et al. 2020

IJMS

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The ability of exogenous low ouabain concentrations to affect claudin expression and therefore epithelial barrier properties was demonstrated previously in cultured cell studies. We hypothesized that chronic elevation of circulating ouabain in vivo can affect the expression of claudins and tight junction permeability in different tissues. We tested this hypothesis in rats intraperitoneally injected with ouabain (1 μg/kg) for 4 days. Rat jejunum, colon and brain frontal lobes, which are variable in the expressed claudins and tight junction permeability, were examined. Moreover, the porcine jejunum cell line IPEC-J2 was studied. In IPEC-J2-cells, ouabain (10 nM, 19 days of incubation) stimulated epithelial barrier formation, increased transepithelial resistance and the level of cSrc-kinase activation by phosphorylation, accompanied with an increased expression of claudin-1, -5 and down-regulation of claudin-12; the expression of claudin-3, -4, -8 and tricellulin was not changed. In the jejunum, chronic ouabain increased the expression of claudin-1, -3 and -5 without an effect on claudin-2 and -4 expression. In the colon, only down-regulation of claudin-3 was observed. Chronic ouabain protected the intestine transepithelial resistance against functional injury induced by lipopolysaccharide treatment or by modeled acute microgravity; this regulation was most pronounced in the jejunum. Сlaudin-1 was also up-regulated in cerebral blood vessels. This was associated with reduction of claudin-3 expression while the expression of claudin-5 and occludin was not affected. Altogether, our results confirm that circulating ouabain can functionally and tissue-specifically affect barrier properties of epithelial and endothelial tissues via Na,K-ATPase-mediated modulation of claudins expression.

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Ouabain Protects Mice Against Lipopolysaccharide-Induced Acute Lung Injury

Cited by 17 publications

References 40 publications

Microarray analysis reveals the changes of circular RNA expression and molecular mechanism in acute lung injury mouse model

Microarray analysis reveals the changes of circular RNA expression and molecular mechanism in acute lung injury mouse model

Na+/K+-ATPase as a Target of Cardiac Glycosides for the Treatment of SARS-CoV-2 Infection

Circulating Ouabain Modulates Expression of Claudins in Rat Intestine and Cerebral Blood Vessels

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