The effect of (prenatal) smoke exposure on lung progenitor cell behavior and Cyp2a5 gene regulation

Khosbayar Lkhagvadorj

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    Lung progenitor cell behavior and Cyp2a5 gene regulation

    Prenatal smoke exposure (PSE) is associated with an increased risk for chronic obstructive pulmonary disease (COPD) and cigarette smoke addiction in later in life. One of the proposed underlying mechanisms for PSE-induced risk for COPD and aberrant smoking behavior could be epigenetic modifications of particular genes.
    UMCG researcher Khosbayar Lkhagvadorj investigated the effect of (prenatal) smoke exposure on lung epithelial cell development and regeneration linked with epidermal growth factor receptor (EGFR) signaling. This was addressed in PSE neonatal mouse offspring and patients with COPD. In addition, he investigated the effect of pre- and/or postnatal smoke exposure on Cyp2a5 DNA methylation in relation to the in vitro nicotine conversion in liver and lung.
    He has provided evidence in mouse and human lung tissue and organoid models that (prenatal) smoke exposure triggers abnormal lung development, tissue regeneration, and nicotine dependence. Firstly, (prenatal) smoke exposure impaired lung epithelial cell differentiation in mouse offspring, which was associated with EGFR signaling. Moreover, lower expression of the EGFR on alveolar type 2 cells could be related to impaired alveolar progenitor cell function in COPD patients, which could explain impaired lung regeneration in these patients. Secondly, PSE increased the nicotine metabolism, which could be linked to a persistent change of PSE-induced Cyp2a5 methylation across the three developmental stages. If our results in the mouse were translated to the human situation, smoking during pregnancy would pose a threat to the unborn child, as it not only affects the development of the fetal lung but may also increase the risk of nicotine addiction when the offspring starts smoking.
    Originele taal-2English
    KwalificatieDoctor of Philosophy
    Toekennende instantie
    • Rijksuniversiteit Groningen
    Begeleider(s)/adviseur
    • Hylkema, Machteld, Supervisor
    • Plosch, Torsten, Supervisor
    Datum van toekenning22-jun-2021
    Plaats van publicatie[Groningen]
    Uitgever
    DOI's
    StatusPublished - 2021

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