IDEAS home Printed from https://ideas.repec.org/a/gam/jijerp/v17y2020i22p8410-d444695.html
   My bibliography  Save this article

Diesel Particulate Matter 2.5 Induces Epithelial-to-Mesenchymal Transition and Upregulation of SARS-CoV-2 Receptor during Human Pluripotent Stem Cell-Derived Alveolar Organoid Development

Author

Listed:
  • Jung-Hyun Kim

    (Department of Internal Medicine, School of Medicine, Kangwon National University, 1 Kangwondaehakgil, Chuncheon 24341, Korea
    Environmental Health Center, Kangwon National University Hospital, Chuncheon 24341, Korea)

  • Jeeyoung Kim

    (Department of Internal Medicine, School of Medicine, Kangwon National University, 1 Kangwondaehakgil, Chuncheon 24341, Korea
    Environmental Health Center, Kangwon National University Hospital, Chuncheon 24341, Korea)

  • Woo Jin Kim

    (Department of Internal Medicine, School of Medicine, Kangwon National University, 1 Kangwondaehakgil, Chuncheon 24341, Korea
    Environmental Health Center, Kangwon National University Hospital, Chuncheon 24341, Korea)

  • Yung Hyun Choi

    (Department of Biochemistry, College of Korean Medicine, Dong-eui University, Busan 47227, Korea)

  • Se-Ran Yang

    (Department of Thoracic and Cardiology, School of Medicine, Kangwon National University, 1 Kangwondaehakgil, Chuncheon 24341, Korea)

  • Seok-Ho Hong

    (Department of Internal Medicine, School of Medicine, Kangwon National University, 1 Kangwondaehakgil, Chuncheon 24341, Korea
    Environmental Health Center, Kangwon National University Hospital, Chuncheon 24341, Korea)

Abstract

Growing evidence links prenatal exposure to particulate matter (PM2.5) with reduced lung function and incidence of pulmonary diseases in infancy and childhood. However, the underlying biological mechanisms of how prenatal PM2.5 exposure affects the lungs are incompletely understood, which explains the lack of an ideal in vitro lung development model. Human pluripotent stem cells (hPSCs) have been successfully employed for in vitro developmental toxicity evaluations due to their unique ability to differentiate into any type of cell in the body. In this study, we investigated the developmental toxicity of diesel fine PM (dPM2.5) exposure during hPSC-derived alveolar epithelial cell (AEC) differentiation and three-dimensional (3D) multicellular alveolar organoid (AO) development. We found that dPM2.5 (50 and 100 μg/mL) treatment disturbed the AEC differentiation, accompanied by upregulation of nicotinamide adenine dinucleotide phosphate oxidases and inflammation. Exposure to dPM2.5 also promoted epithelial-to-mesenchymal transition during AEC and AO development via activation of extracellular signal-regulated kinase signaling, while dPM2.5 had no effect on surfactant protein C expression in hPSC-derived AECs. Notably, we provided evidence, for the first time, that angiotensin-converting enzyme 2, a receptor to mediate the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) entry into target cells, and the cofactor transmembrane protease serine 2 were significantly upregulated in both hPSC-AECs and AOs treated with dPM2.5. In conclusion, we demonstrated the potential alveolar development toxicity and the increase of SARS-Cov-2 susceptibility of PM2.5. Our findings suggest that an hPSC-based 2D and 3D alveolar induction system could be a useful in vitro platform for evaluating the adverse effects of environmental toxins and for virus research.

Suggested Citation

  • Jung-Hyun Kim & Jeeyoung Kim & Woo Jin Kim & Yung Hyun Choi & Se-Ran Yang & Seok-Ho Hong, 2020. "Diesel Particulate Matter 2.5 Induces Epithelial-to-Mesenchymal Transition and Upregulation of SARS-CoV-2 Receptor during Human Pluripotent Stem Cell-Derived Alveolar Organoid Development," IJERPH, MDPI, vol. 17(22), pages 1-15, November.
    • Handle: RePEc:gam:jijerp:v:17:y:2020:i:22:p:8410-:d:444695
    as

    Download full text from publisher

    File URL: https://www.mdpi.com/1660-4601/17/22/8410/pdf
    Download Restriction: no
    File URL: https://www.mdpi.com/1660-4601/17/22/8410/
    Download Restriction: no
    ---><---

    References listed on IDEAS

    as
    1. Yumiko Imai & Keiji Kuba & Shuan Rao & Yi Huan & Feng Guo & Bin Guan & Peng Yang & Renu Sarao & Teiji Wada & Howard Leong-Poi & Michael A. Crackower & Akiyoshi Fukamizu & Chi-Chung Hui & Lutz Hein & S, 2005. "Angiotensin-converting enzyme 2 protects from severe acute lung failure," Nature, Nature, vol. 436(7047), pages 112-116, July.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Alberto Izzotti & Paola Spatera & Zumama Khalid & Alessandra Pulliero, 2022. "Importance of Punctual Monitoring to Evaluate the Health Effects of Airborne Particulate Matter," IJERPH, MDPI, vol. 19(17), pages 1-18, August.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Steven Andrew Baker & Shirley Kwok & Gerald J Berry & Thomas J Montine, 2021. "Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation," PLOS ONE, Public Library of Science, vol. 16(2), pages 1-17, February.
    2. Sara, Raisa & Radoias, Vlad & Kim, Younoh, 2024. "Hypertension effects of the COVID-19 lockdowns: Evidence from a repeated cross-sectional survey in Peru," Economics & Human Biology, Elsevier, vol. 52(C).
    3. Milad Haghani & Pegah Varamini, 2021. "Temporal evolution, most influential studies and sleeping beauties of the coronavirus literature," Scientometrics, Springer;Akadémiai Kiadó, vol. 126(8), pages 7005-7050, August.
    4. Tomokazu Yamaguchi & Midori Hoshizaki & Takafumi Minato & Satoru Nirasawa & Masamitsu N. Asaka & Mayumi Niiyama & Masaki Imai & Akihiko Uda & Jasper Fuk-Woo Chan & Saori Takahashi & Jianbo An & Akari , 2021. "ACE2-like carboxypeptidase B38-CAP protects from SARS-CoV-2-induced lung injury," Nature Communications, Nature, vol. 12(1), pages 1-13, December.

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:gam:jijerp:v:17:y:2020:i:22:p:8410-:d:444695. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: MDPI Indexing Manager (email available below). General contact details of provider: https://www.mdpi.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.