scholarly journals Human bronchial epithelial cell‐derived extracellular vesicle therapy for pulmonary fibrosis via inhibition of TGF‐β‐WNT crosstalk

2021 ◽  
Vol 10 (10) ◽  
Author(s):  
Tsukasa Kadota ◽  
Yu Fujita ◽  
Jun Araya ◽  
Naoaki Watanabe ◽  
Shota Fujimoto ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Pulmonary Fibrosis ◽  
Extracellular Vesicle ◽  
Bronchial Epithelial Cell ◽  
Human Bronchial Epithelial Cell ◽  
Bronchial Epithelial

scholarly journals Human bronchial epithelial cell-derived extracellular vesicle therapy for pulmonary fibrosis via inhibition of TGF-β-WNT crosstalk

2020 ◽  
Author(s):  
Tsukasa Kadota ◽  
Yu Fujita ◽  
Jun Araya ◽  
Naoaki Watanabe ◽  
Shota Fujimoto ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Pulmonary Fibrosis ◽  
Wnt Signaling ◽  
Cellular Senescence ◽  
Bronchial Epithelial Cell ◽  
Human Bronchial Epithelial Cell ◽  
Bioactive Molecules ◽  
Myofibroblast Differentiation ◽  
Intratracheal Administration ◽  
Bronchial Epithelial

AbstractIdiopathic pulmonary fibrosis (IPF) is characterized by devastating and progressive lung parenchymal fibrosis, resulting in poor patient prognosis. An aberrant recapitulation of developmental lung gene expression, including genes for transforming growth factor (TGF)-β and WNT, has been widely implicated in the pathogenic IPF wound healing process that results from repetitive alveolar epithelial injury. Extracellular vesicles (EVs) have been shown to carry bioactive molecules and to be involved in various physiological and pathological processes. Here, we demonstrate that, by attenuating WNT signaling, human bronchial epithelial cell-derived EVs (HBEC EVs) inhibit TGF-β mediated induction of both myofibroblast differentiation and lung epithelial cellular senescence. This effect of HBEC EVs is more pronounced than that observed with mesenchymal stem cell-derived EVs. Mechanistically, the HBEC EV microRNA (miRNA) cargo is primarily responsible for attenuating both myofibroblast differentiation and cellular senescence. This attenuation occurs via inhibition of canonical and non-canonical WNT signaling pathways. Among enriched miRNA species present in HBEC EVs, miR-16, miR-26a, miR-26b, miR-141, miR-148a, and miR-200a are mechanistically involved in reducing WNT5A and WNT10B expression in LFs, and in reducing WNT3A, WNT5A, and WNT10B expression in HBECs. Mouse models utilizing intratracheal administration of EVs demonstrate efficient attenuation of bleomycin-induced lung fibrosis development accompanied by reduced expression of both β-catenin and markers of cellular senescence. These findings indicate that EVs derived from normal resident lung HBECs may possess anti-fibrotic properties. They further suggest that, via miRNA-mediated inhibition of TGF-β-WNT crosstalk, HBEC EVs administration can be a promising anti-fibrotic modality of treatment for IPF.

Retinoic acid inhibits interleukin-4-induced eotaxin production in a human bronchial epithelial cell line

2004 ◽  
Vol 286 (4) ◽  
pp. L777-L785 ◽  
Author(s):  
Kei Takamura ◽  
Yasuyuki Nasuhara ◽  
Motoko Kobayashi ◽  
Tomoko Betsuyaku ◽  
Yoko Tanino ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Epithelial Cell ◽  
Cell Line ◽  
Nuclear Translocation ◽  
Bronchial Epithelial Cell ◽  
Inhibitory Effect ◽  
Human Bronchial Epithelial Cell ◽  
Epithelial Cell Line ◽  
Transcriptional Level ◽  
Bronchial Epithelial

Retinoic acid (RA) is known to accelerate wound healing and induce cell differentiation. All- trans RA (ATRA) exerts its effect by binding retinoic acid receptors, which are members of the nuclear receptor family. We investigated whether RA can alter expression of eotaxin, a potent eosinophil chemoattractant that is regulated by the transcription factors signal transducer and activator of transcription 6 (STAT6) and NF-κB. We examined the effects of RA on eotaxin expression in a human bronchial epithelial cell line BEAS-2B. ATRA and its stereodimer 9- cis retinoic acid (9- cis RA) inhibited IL-4-induced release of eotaxin at 10-6M by 78.0 and 52.0%, respectively ( P < 0.05). ATRA and 9- cis RA also significantly inhibited IL-4-induced eotaxin mRNA expression at 10-6M by 52.3 and 53.5%, respectively ( P < 0.05). In contrast, neither ATRA nor 9- cis RA had any effects on TNF-α-induced eotaxin production. In transfection studies using eotaxin promoter luciferase plasmids, the inhibitory effect of ATRA on IL-4-induced eotaxin production was confirmed at the transcriptional level. Interestingly, ATRA had no effects on IL-4-induced tyrosine phosphorylation, nuclear translocation, or DNA binding activity of STAT6. Activating protein-1 was not involved in ATRA-mediated transrepression of eotaxin with IL-4 stimulation. The mechanism of the inhibitory effect of ATRA on IL-4-induced eotaxin production in human bronchial epithelial cells has not been elucidated but does not appear to be due to an effect on STAT6 activation. These findings raise the possibility that RA may reduce eosinophilic airway inflammation, one of the prominent pathological features of allergic diseases such as bronchial asthma.

scholarly journals A Comparative Study on the Model of PM2.5 Direct or Indirect Interaction with Bronchial Epithelial Cells.

2021 ◽  
Author(s):  
Yan Wang ◽  
Xin Zuo ◽  
Fuyang Jiang ◽  
Lin Hou ◽  
Qiyue Jiang ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Cell Damage ◽  
Direct Interaction ◽  
Bronchial Epithelial Cell ◽  
Human Bronchial Epithelial Cell ◽  
Exposure Model ◽  
Epithelial Cell Line ◽  
Bronchial Epithelial ◽  
The Impact

Abstract The impact of PM2.5 on epithelial cells is a pivotal process leading to many lung pathological changes and pulmonary diseases. In addition to PM2.5 direct interaction with epithelia, macrophages that engulf PM2.5 may also influence the function of epithelial cells. However, among the toxic researches of PM2.5, there is a lack of evaluation of direct or indirect exposure model on human bronchial epithelial cell against PM2.5. In this present research, PM2.5-exposed human bronchial epithelial cell line (BEAS-2B) serves as the direct interaction model, while the contrast is to indirect stimulation model, which takes advantage of transwell co-culture system to carry out that PM2.5 is promptly contacted with macrophages rather than BEAS-2B. By comparing these two modes of interaction, we determined the viability of BEAS-2B and mRNA and/or protein expression profile of transcription factors Nrf2,NF-kB and according inflammatory indicators, with a view to evaluating the effects of different interaction modes of PM2.5 on epithelial cell damage in vitro. We have found that macrophage involvement may protect epithelia from PM2.5 cytotoxic effect, while strengthen the inflammation response.

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