• Am. J. Physiol. Lung Cell Mol. Physiol. · Apr 2020

    Adipose-derived exosomes protect the pulmonary endothelial barrier in ventilator-induced lung injury by inhibiting the TRPV4/Ca2+ signaling pathway.

    • Qian Yu, Daoxin Wang, Xiaoting Wen, Xumao Tang, Di Qi, Jing He, Yan Zhao, Wang Deng, and Tao Zhu.
    • Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
    • Am. J. Physiol. Lung Cell Mol. Physiol. 2020 Apr 1; 318 (4): L723-L741.

    AbstractMechanical ventilation (MV) is the main supportive treatment of acute respiratory distress syndrome (ARDS), but it may lead to ventilator-induced lung injury (VILI). Large epidemiological studies have found that obesity was associated with lower mortality in mechanically ventilated patients with acute lung injury, which is known as "obesity paradox." However, the effects of obesity on VILI are unknown. In the present study, wild-type mice were fed a high-fat diet (HFD) and ventilated with high tidal volume to investigate the effects of obesity on VILI in vivo, and pulmonary microvascular endothelial cells (PMVECs) were subjected to 18% cyclic stretching (CS) to further investigate its underlying mechanism in vitro. We found that HFD protects mice from VILI by alleviating the pulmonary endothelial barrier injury and inflammatory responses in mice. Adipose-derived exosomes can regulate distant tissues as novel adipokines, providing a new mechanism for cell-cell interactions. We extracted three adipose-derived exosomes, including HFD mouse serum exosome (S-Exo), adipose tissue exosome (AT-Exo), and adipose-derived stem cell exosome (ADSC-Exo), and further explored their effects on MV or 18% CS-induced VILI in vivo and in vitro. Administration of three exosomes protected against VILI by suppressing pulmonary endothelial barrier hyperpermeability, repairing the expression of adherens junctions, and alleviating inflammatory response in vivo and in vitro, accompanied by transient receptor potential vanilloid 4 (TRPV4)/Ca2+ pathway inhibition. Collectively, these data indicated that HFD-induced obesity plays a protective role in VILI by alleviating the pulmonary endothelial barrier injury and inflammatory response via adipose-derived exosomes, at least partially, through inhibiting the TRPV4/Ca2+ pathway.

      Pubmed     Free full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…