• Cells · Sep 2019

    Mesenchymal WNT-5A/5B Signaling Represses Lung Alveolar Epithelial Progenitors.

    • Xinhui Wu, Eline M van Dijk, John-Poul Ng-Blichfeldt, Bos I Sophie T IST Department of Molecular Pharmacology, Faculty of Science and Engineering, University of Groningen, Antonius Deusinglaan 1, 9713AV Groningen, The Nether, Chiara Ciminieri, Melanie Königshoff, Kistemaker Loes E M LEM Department of Molecular Pharmacology, Faculty of Science and Engineering, University of Groningen, Antonius Deusinglaan 1, 9713AV Groningen, The N, and Reinoud Gosens.
    • Department of Molecular Pharmacology, Faculty of Science and Engineering, University of Groningen, Antonius Deusinglaan 1, 9713AV Groningen, The Netherlands. x.wu@rug.nl.
    • Cells. 2019 Sep 25; 8 (10).

    AbstractChronic obstructive pulmonary disease (COPD) represents a worldwide concern with high morbidity and mortality, and is believed to be associated with accelerated ageing of the lung. Alveolar abnormalities leading to emphysema are a key characteristic of COPD. Pulmonary alveolar epithelial type 2 cells (AT2) produce surfactant and function as progenitors for type 1 cells. Increasing evidence shows elevated WNT-5A/B expression in ageing and in COPD that may contribute to the disease process. However, supportive roles for WNT-5A/B in lung regeneration were also reported in different studies. Thus, we explored the role of WNT-5A/B on alveolar epithelial progenitors (AEPs) in more detail. We established a Precision-Cut-Lung Slices (PCLS) model and a lung organoid model by co-culturing epithelial cells (EpCAM+/CD45-/CD31-) with fibroblasts in matrigel in vitro to study the impact of WNT-5A and WNT-5B. Our results show that WNT-5A and WNT-5B repress the growth of epithelial progenitors with WNT-5B preferentially restraining the growth and differentiation of alveolar epithelial progenitors. We provide evidence that both WNT-5A and WNT-5B negatively regulate the canonical WNT signaling pathway in alveolar epithelium. Taken together, these findings reveal the functional impact of WNT-5A/5B signaling on alveolar epithelial progenitors in the lung, which may contribute to defective alveolar repair in COPD.

      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…