scholarly journals P16‐13: Bronchial epithelial cell‐derived extracellular vesicles attenuate pulmonary fibrosis targeting TGF‐Β‐WNT crosstalk

Respirology ◽  
2021 ◽  
Vol 26 (S3) ◽  
pp. 453-453
Keyword(s):  
Epithelial Cell ◽  
Pulmonary Fibrosis ◽  
Extracellular Vesicles ◽  
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.

scholarly journals Essential Role of Visfatin in Lipopolysaccharide and Colon Ascendens Stent Peritonitis-Induced Acute Lung Injury

2019 ◽  
Vol 20 (7) ◽  
pp. 1678 ◽  
Author(s):  
Yi-Chen Lee ◽  
Chun-Yu Lin ◽  
Yen-Hsu Chen ◽  
Wen-Chin Chiu ◽  
Yen-Yun Wang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Epithelial Cell ◽  
Lung Injury ◽  
Cell Lines ◽  
Inflammatory Cytokines ◽  
Bronchial Epithelial Cell ◽  
Bronchial Epithelial ◽  
Epithelial Cell Lines ◽  
Nfκb Pathway ◽  
Pro Inflammatory Cytokines

Acute lung injury (ALI) is a life-threatening syndrome characterized by acute and severe hypoxemic respiratory failure. Visfatin, which is known as an obesity-related cytokine with pro-inflammatory activities, plays a role in regulation of inflammatory cytokines. The mechanisms of ALI remain unclear in critically ill patients. Survival in ALI patients appear to be influenced by the stress generated by mechanical ventilation and by ALI-associated factors that initiate the inflammatory response. The objective for this study was to understand the mechanisms of how visfatin regulates inflammatory cytokines and promotes ALI. The expression of visfatin was evaluated in ALI patients and mouse sepsis models. Moreover, the underlying mechanisms were investigated using human bronchial epithelial cell lines, BEAS-2B and NL-20. An increase of serum visfatin was discovered in ALI patients compared to normal controls. Results from hematoxylin and eosin (H&E) and immunohistochemistry staining also showed that visfatin protein was upregulated in mouse sepsis models. Moreover, lipopolysaccharide (LPS) induced visfatin expression, activated the STAT3/NFκB pathway, and increased the expression of pro-inflammatory cytokines, including IL1-β, IL-6, and TNF-α in human bronchial epithelial cell lines NL-20 and BEAS-2B. Co-treatment of visfatin inhibitor FK866 reversed the activation of the STAT3/NFκB pathway and the increase of pro-inflammatory cytokines induced by LPS. Our study provides new evidence for the involvement of visfatin and down-stream events in acute lung injury. Further studies are required to confirm whether the anti-visfatin approaches can improve ALI patient survival by alleviating the pro-inflammatory process.

Expressional pattern of chaperones in neuronal, glial, amnion, mesothelial, and bronchial epithelial cell lines

2003 ◽  
Vol 80 (4) ◽  
pp. 444-450 ◽  
Author(s):  
Jae-Kyung Myung ◽  
Kurt Krapfenbauer ◽  
Rachel Weitzdoerfer ◽  
Andreas Peyrl ◽  
Michael Fountoulakis ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Lines ◽  
Bronchial Epithelial Cell ◽  
Bronchial Epithelial ◽  
Epithelial Cell Lines
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