The role of accelerated ageing in aberrant lung tissue repair and remodelling in COPD

    Research output: ThesisThesis fully internal (DIV)

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    Abstract

    Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, while the prevalence is still increasing. Since the exact pathogenesis is still unknown and no therapeutics are available to stop disease progression, novel insights into the pathogenesis are needed. Recently, accelerated ageing has been postulated to play a role in COPD and extracellular matrix (ECM) dysregulation has been described as a hallmark of lung ageing. ECM dysregulation can cause aberrant tissue repair and remodelling. The aim of this thesis was to elucidate the role of accelerated ageing in aberrant tissue repair and remodelling in COPD.
    We analysed ageing markers in lung fibroblasts and airway smooth muscle cells (ASMCs) from COPD patients compared to matched controls and we assessed the functional effects of senescence induction.
    We found characteristics of accelerated ageing in COPD-derived fibroblasts compared to controls, including higher levels of cellular senescence. The increase in senescence in COPD-derived fibroblasts was associated with lower levels of the ECM protein decorin and higher levels of pro-inflammatory protein secretion. Induction of senescence also resulted in ECM changes, secretion of pro-inflammatory proteins and impaired tissue repair. Furthermore, ASMCs had higher levels of senescence than lung fibroblasts, but in ASMCs no differences were found between COPD and control. Finally, we showed that E-cigarette extract induces senescence in lung fibroblasts and concluded that E-cigarettes are not a safe smoking alternative.
    These studies indicate that accelerated ageing plays a role in aberrant tissue repair and remodelling in COPD and thereby contributes to the pathogenesis.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Brandsma, Corry-Anke, Supervisor
    • Oliver, B.G., Supervisor, External person
    • Timens, Wim, Supervisor
    • Heijink, Irene, Supervisor
    Award date29-Jun-2021
    Place of Publication[Groningen]
    Publisher
    DOIs
    Publication statusPublished - 2021

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