Intermedin Reduces Oxidative Stress and Apoptosis in Ventilator-Induced Lung Injury via JAK2/STAT3

Fan, Shulei; He, Jing; Yang, Yanli; Wang, Daoxin

doi:10.3389/fphar.2021.817874

Cited by 10 publications

(6 citation statements)

References 44 publications

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“…ROS can modulate a number of cell signaling pathways, including the JAK2–STAT3 pathway ( 19 , 20 ). STAT3 is a transcription factor, which serves a pivotal role in tumor cell proliferation and progression ( 21 ).…”

Section: Resultsmentioning

confidence: 99%

Mebendazole induces apoptosis and inhibits migration via the reactive oxygen species-mediated STAT3 signaling downregulation in non-small cell lung cancer

Liang,

Chen,

Pan

et al. 2024

J Thorac Dis

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Background The incidence and mortality of non-small cell lung cancer (NSCLC) are extremely high. Previous research has confirmed that the signal transducer and activator of the transcription 3 (STAT3) protein critically participate in the tumorigenesis of NSCLC. Mebendazole (MBZ) has exerts a larger number of pharmacological activities and has anticancer effects in lung cancer, but its mechanism of action remains unclear. This study thus aimed to clarify the impacts of MBZ on NSCLC cell. Methods Cell proliferation, migration, and apoptosis were investigated via cell counting kit 8 (CCK-8) assay, Transwell assay, colony formation assay, wound-healing assay, and flow cytometry. Reactive oxygen species (ROS) were detected with a multifunctional microplate reader. Markers of cell migration and apoptosis were detected with Western blotting. The transcriptional activity of STAT3 was detected via luciferase assay. ROS scavenger N-acetylcysteine (NAC) was used to determine the effect of MBZ on NSCLC via ROS-regulated STAT3 inactivation and apoptosis. A xenograft model was constructed in vivo to investigate the role of MBZ in NSCLC tumor growth. Results The findings demonstrated that MBZ inhibited NSCLC cell proliferation and migration while promoting apoptosis through triggering ROS generation. In addition, the Janus kinase 2 (JAK2)-STAT3 signaling pathway was abrogated with the treatment of MBZ. NAC could distinctly weaken MBZ-induced apoptosis and STAT3 inactivation. Moreover, MBZ inhibited the tumor growth of NSCLC in vivo . Conclusions In summary, MBZ inhibited NSCLC cell viability and migration by inducing cell apoptosis via the ROS-JAK2-STAT3 signaling pathway. These data provide a theoretical basis for the use of MBZ in treating NSCLC.

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Section: Resultsmentioning

confidence: 99%

Mebendazole induces apoptosis and inhibits migration via the reactive oxygen species-mediated STAT3 signaling downregulation in non-small cell lung cancer

Liang,

Chen,

Pan

et al. 2024

J Thorac Dis

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“…Therefore, VILI is also considered as a biological injury [2,23]. Relevant studies have shown that JAK2-STAT3, PI3/Akt, NF-κB, p38/MAPK, and other signaling pathways can mediate inflammation and/or apoptosis and act on VILI progression [20,[24][25][26][27]. However, it is still necessary to explore the key points in the pathogenesis network of VILI.…”

Section: Discussionmentioning

confidence: 99%

“…DMSO as placebo and SB216763 as GSK-3β inhibitor (MedChemExpress, Shanghai, China). They were transfected into cells by Lipofectamine 3000 reagent (Thermo Fisher Scientific, U.S.A.) before cyclic stretching with Flexcell Tension PluFX-4000TM (Flexcell International Corporation, Burlington, U.S.A.) [20].…”

Section: Cell Experimentsmentioning

confidence: 99%

The Wnt/β-catenin pathway regulates inflammation and apoptosis in ventilator-induced lung injury

Chen

Lian

et al. 2023

Bioscience Reports

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Ventilator-induced lung injury (VILI) may be caused by incorrect mechanical ventilation (MV), and its progression is mainly related to inflammatory reaction, apoptosis and oxidative stress. The Wnt/β-catenin pathway can modulate inflammation and apoptosis, however, its role in VILI is unknown. This research aims to explore the role of the Wnt/β-catenin pathway in VILI. VILI models were established using rats and type II alveolar epithelial cells. GSK-3β, β-catenin and cyclin D1 were determined using western blot and immunofluorescence. Apoptosis of lung tissues was evaluated using TUNEL, flow cytometry, Bax and Bcl2 protein. IL-1β, IL-6 and TNF-α were detected via ELISA. Lung pathological injury was evaluated through hematoxylin and eosin staining. Lung permeability was evaluated by the ratio of dry to wet weight of lung tissue and the total protein level of bronchoalveolar lavage fluid. The results showed that GSK-3β expression was enhanced and β-catenin expression was diminished in lung tissue under MV. SB216763 increased β-catenin and cyclin D1 expression by inhibiting GSK-3β expression and inhibited the inflammatory response and apoptosis of lung, alleviated pulmonary edema and lung tissue permeability, and significantly mitigated lung injury. However, inhibition of β-catenin expression by MSAB attenuated the anti-inflammatory and anti-apoptotic effects of SB216763 in VILI. Overall, this study demonstrates that the Wnt/β-catenin pathway activation in MV may play an anti-inflammatory and anti-apoptotic role, thereby alleviating lung injury and delaying VILI progression, which may be a key point of intervention in VILI.

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“…Apoptosis of lung cells plays a pivotal role in ALI/ARDS development [ 55 , 56 ]. Therefore, it is urgent to solve the problem of apoptosis in ALI/ARDS.…”

Section: Discussionmentioning

confidence: 99%

Integrated metabolomics, network pharmacology and biological verification to reveal the mechanisms of Nauclea officinalis treatment of LPS-induced acute lung injury

Han

et al. 2022

Chin Med

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Background Acute lung injury (ALI) is a severe inflammatory disease, underscoring the urgent need for novel treatments. Nauclea officinalis Pierre ex Pitard (Danmu in Chinese, DM) is effective in treating inflammatory respiratory diseases. However, there is still no evidence of its protective effect against ALI. Methods Metabolomics was applied to identify the potential biomarkers and pathways in ALI treated with DM. Further, network pharmacology was introduced to predict the key targets of DM against ALI. Then, the potential pathways and key targets were further verified by immunohistochemistry and western blot assays. Results DM significantly improved lung histopathological characteristics and inflammatory response in LPS-induced ALI. Metabolomics analysis showed that 16 and 19 differential metabolites were identified in plasma and lung tissue, respectively, and most of these metabolites tended to recover after DM treatment. Network pharmacology analysis revealed that the PI3K/Akt pathway may be the main signaling pathway of DM against ALI. The integrated analysis of metabolomics and network pharmacology identified 10 key genes. These genes are closely related to inflammatory response and cell apoptosis of lipopolysaccharide (LPS)-induced ALI in mice. Furthermore, immunohistochemistry and western blot verified that DM could regulate inflammatory response and cell apoptosis by affecting the PI3K/Akt pathway, and expression changes in Bax and Bcl-2 were also triggered. Conclusion This study first integrated metabolomics, network pharmacology and biological verification to investigate the potential mechanism of DM in treating ALI, which is related to the regulation of inflammatory response and cell apoptosis. And the integrated analysis can provide new strategies and ideas for the study of traditional Chinese medicines in the treatment of ALI. Graphical Abstract

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Intermedin Reduces Oxidative Stress and Apoptosis in Ventilator-Induced Lung Injury via JAK2/STAT3

Cited by 10 publications

References 44 publications

Mebendazole induces apoptosis and inhibits migration via the reactive oxygen species-mediated STAT3 signaling downregulation in non-small cell lung cancer

Mebendazole induces apoptosis and inhibits migration via the reactive oxygen species-mediated STAT3 signaling downregulation in non-small cell lung cancer

The Wnt/β-catenin pathway regulates inflammation and apoptosis in ventilator-induced lung injury

Integrated metabolomics, network pharmacology and biological verification to reveal the mechanisms of Nauclea officinalis treatment of LPS-induced acute lung injury

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