Air pollution-regulated E-cadherin mediates contact inhibition of proliferation via the hippo signaling pathways in emphysema

Chang, Jer‐Hwa; Lee, Yueh-Lun; Laiman, Vincent; Han, Chia Li; Jheng, Yu-Teng; Lee, Kang‐Yun; Yeh, Chi‐Tai; Kuo, Han‐Pin; Chung, Kian Fan; Heriyanto, Didik Setyo; Hsiao, Ta-Chih; Wu, Sheng‐Ming; Ho, Shu-Chuan; Chuang, Kai Jen; Chuang, Hsiao-Chi

doi:10.1016/j.cbi.2021.109763

Cited by 9 publications

(2 citation statements)

References 52 publications

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“…Therefore, to further investigate the effect of BFP-TA on gene expression in CSE-induced Beas-2B cells, Illumina sequencing technology was used to perform transcriptome sequencing, bioinformatic analysis, screening of DEGs, systematic analysis of the relevant biological functions and possible mechanism to search for possible target genes for the treatment of COPD. Subsequently, KEGG enrichment analysis revealed multiple pathways associated with COPD, including p53 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, Hippo signaling pathway, Nicotine addiction, PPAR signaling pathway, Cholesterol metabolism, etc., which was consistent with previous studies (33)(34)(35)(36)(37)(38), and could initially confirm the reliability of this study. Among the top 20 signaling pathways enriched based on key DEGs, we are most interested in the PPAR signaling pathway and the PI3K-Akt signaling pathway.…”

Section: Discussionsupporting

confidence: 93%

Protective effect of the total alkaloid extract from Bulbus Fritillariae Pallidiflorae on cigarette smoke-induced Beas-2B cell injury model and transcriptomic analysis

Wang,

Liu,

AGA

et al. 2024

Food & Nutrition Research

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Background: Bulbus Fritillariae Pallidiflorae (BFP) is a traditional Chinese medicine that has long been used to treat lung diseases, but the active components and mechanism are still unclear. Objective: This study aimed to investigate the effect and mechanism of the total alkaloid extract from BFP (BFP-TA) on cigarette smoke extract (CSE)-induced Beas-2B cells injury. Design: The Beas-2B cells injury model was induced by 2% CSE, then the effect of BFP-TA on the levels of total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and malondialdehyde (MDA) was detected according to the instructions of the T-AOC assay kit, the SOD detection kit and the MDA detection kit, and the production of ROS was detected by fluorescence microscopy. The effect of BFP-TA on Beas-2B cells apoptosis was detected by flow cytometry, and the effect of BFP-TA on related protein expression was detected by western blot. Subsequently, the effect of BFP-TA on differentially expressed genes (DEGs) in CSE-induced Beas-2B cells was studied by transcriptomic sequencing, and the expression of DEGs was verified by quantitative real-time polymerase chain reaction (qPCR). Results: The results showed that BFP-TA could attenuate CSE-induced oxidative damage in Beas-2B cells by elevating T-AOC and SOD levels while inhibiting ROS and MDA levels, and the mechanism was potentially related to the SIRT1/Nrf2/Keap1 signaling pathway. Furthermore, BFP-TA could inhibit CSE-induced apoptosis by inhibiting the protein expression of Bax, MST1 and FOXO3a, and exert anti-inflammatory effect by inhibiting the activation of MAPK signaling pathway. Subsequently, transcriptome analysis and qPCR validation showed that BFP-TA could alleviate inflammation, oxidative stress, apoptosis and lipid metabolism disorders by regulating the expression of DEGs in PPAR and PI3K-Akt signaling pathways, thereby exerting a protective effect against CSE-induced Beas-2B cell injury. Conclusion: This study is the first to demonstrate that BFP-TA could exert a protective effect on CSE-induced Beas-2B cell injury by exerting anti-inflammatory, antioxidant, anti-apoptotic and regulate lipid metabolism disorders.

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Section: Discussionsupporting

confidence: 93%

Protective effect of the total alkaloid extract from Bulbus Fritillariae Pallidiflorae on cigarette smoke-induced Beas-2B cell injury model and transcriptomic analysis

Wang,

Liu,

AGA

et al. 2024

Food & Nutrition Research

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“…Next, we observed decreased phosphorylation of Yap in AECII of this PPE-induced emphysema mouse model. Similarly, our previous study on an emphysema mouse model by air pollution also showed decreased Yap phosphorylation [43]. A previous study on mice with intranasal pneumococcal infection also found that infection increased AECII Yap nuclear activity [19].…”

Section: Discussionsupporting

confidence: 72%

Reduction of Emphysema Severity by Human Umbilical Cord-Derived Mesenchymal Stem Cells in Mice

Laiman

Lee

Hou

et al. 2022

IJMS

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Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in chronic lung disease patients throughout the world. Mesenchymal stem cells (MSCs) have been shown to regulate immunomodulatory, anti-inflammatory, and regenerative responses. However, the effects of human-umbilical-cord-derived mesenchymal stem cells (hUC-MSCs) on the lung pathophysiology of COPD remain unclear. We aimed to investigate the role of hUC-MSCs in emphysema severity and Yes-associated protein (Yap) phosphorylation (p-Yap) in a porcine-pancreatic-elastase (PPE)-induced emphysema model. We observed that the emphysema percentages (normalized to the total lung volume) measured by chest computed tomography (CT) and exercise oxygen desaturation were significantly reduced by hUC-MSCs at 107 cells/kg body weight (BW) via intravenous administration in emphysematous mice (p < 0.05). Consistently, the emphysema index, as assessed by the mean linear intercept (MLI), significantly decreased with hUC-MSC administration at 3 × 106 and 107 cells/kg BW (p < 0.05). Changes in the lymphocytes, monocytes, and splenic cluster of differentiation 4-positive (CD4+) lymphocytes by PPE were significantly reversed by hUC-MSC administration in emphysematous mice (p < 0.05). An increasing neutrophil/lymphocyte ratio was reduced by hUC-MSCs at 3 × 106 and 107 cells/kg BW (p < 0.05). The higher levels of tumor necrosis factor (TNF)-α, keratinocyte chemoattractant (KC), and lactate dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF) were significantly decreased by hUC-MSC administration (p < 0.05). A decreasing p-Yap/Yap ratio in type II alveolar epithelial cells (AECII) of mice with PPE-induced emphysema was significantly increased by hUC-MSCs (p < 0.05). In conclusion, the administration of hUC-MSCs improved multiple pathophysiological features of mice with PPE-induced emphysema. The effectiveness of the treatment of pulmonary emphysema with hUC-MSCs provides an essential and significant foundation for future clinical studies of MSCs in COPD patients.

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Importance of surface charge of soot nanoparticles in determining inhalation toxicity in mice

Hsiao

Han

Yang

et al. 2022

Environ Sci Pollut Res

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Air pollution-regulated E-cadherin mediates contact inhibition of proliferation via the hippo signaling pathways in emphysema

Cited by 9 publications

References 52 publications

Protective effect of the total alkaloid extract from Bulbus Fritillariae Pallidiflorae on cigarette smoke-induced Beas-2B cell injury model and transcriptomic analysis

Protective effect of the total alkaloid extract from Bulbus Fritillariae Pallidiflorae on cigarette smoke-induced Beas-2B cell injury model and transcriptomic analysis

Reduction of Emphysema Severity by Human Umbilical Cord-Derived Mesenchymal Stem Cells in Mice

Importance of surface charge of soot nanoparticles in determining inhalation toxicity in mice

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