Publication

MicroRNAs as regulators of lung homeostasis, abnormal repair and ageing

Ong, J., 2019, [Groningen]: Rijksuniversiteit Groningen. 169 p.

Research output: ThesisThesis fully internal (DIV)Academic

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  • Title and contents

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  • Chapter 1

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  • Chapter 2

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  • List of publications

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  • Complete thesis

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  • Propositions

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In this thesis, we hypothesized that microRNAs (miRNAs) with deregulated expression in lung fibroblasts, are crucial players in the impaired lung tissue repair and remodelling as observed in chronic obstructive pulmonary disease (COPD). To explore this, we focused on miRNA expression changes in the lung, and in particular in fibroblasts in relation to the effects of TGF-β, and current smoking and associations with COPD and ageing. We identified 106 TGF-β-regulated miRNAs in control and/or in COPD lung fibroblasts. Of these, three miRNAs responded differently to TGF-β in COPD compared to control lung fibroblasts. Only one miRNA was higher expressed in COPD compared to control lung fibroblasts. Furthermore, we identified one miRNA that was lower expressed in lung fibroblasts from current compared to ex-smokers. We identified >960 genes that are actively regulated by miRNAs in lung fibroblasts, which were used to identify fibroblast-specific targets of the differentially expressed miRNAs. Our studies indicate that the identified miRNAs may affect the function of lung fibroblasts through these genes, and affect tissue repair and remodelling, and thus are implicated in COPD pathogenesis. In bronchial biopsies of healthy control subjects, 285 age-related genes and 27 age-related miRNAs were identified. Genes with lower expression with increasing age included several hallmarks of ageing whereas genes with higher expression with increasing age were amongst others involved in synapse-related processes. These studies provide a good stepping stone for further studies aiming to clarify the complex role of these miRNAs in relation to abnormal tissue repair in COPD and ageing.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
Supervisors/Advisors
Award date24-Jun-2019
Place of Publication[Groningen]
Publisher
Print ISBNs978-94-034-1714-1
Electronic ISBNs978-94-034-1713-4
Publication statusPublished - 2019

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