MicroRNA-34a drives small airway fibroblast cellular senescence in COPD

Wrench, Catherine; Baker, Jonathan; Fenwick, Peter; Donnelly, Louise; Barnes, Peter J.

doi:10.1183/1393003.congress-2017.oa289

Cited by 3 publications

(3 citation statements)

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“…A similar increase in senescence of the smooth muscle that surrounds pulmonary arteries in these patients was also observed, providing further links between vascular senescence, atherosclerosis and COPD [69]. Small sections of regulatory RNA, known as microRNAs (miRs) have been implicated in promoting cellular senescence and miR-34a has been associated with fibroblast senescence in COPD [70] atherosclerosis [71] and T2D [72], demonstrating a common link between diseases.…”

Section: Theme 1: Accelerated Ageing In Multimorbiditysupporting

confidence: 53%

Shared mechanisms of multimorbidity in COPD, atherosclerosis and type-2 diabetes: the neutrophil as a potential inflammatory target

2020

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Multimorbidity is increasingly common and current healthcare strategies are not always aligned to treat this complex burden of disease. COPD, type-2 diabetes mellitus (T2D) and cardiovascular disease, especially atherosclerosis, occur more frequently together than expected, even when risk factors such as smoking, obesity, inactivity and poverty are considered. This supports the possibility of unifying mechanisms that contribute to the pathogenesis or progression of each condition.Neutrophilic inflammation is causally associated with COPD, and increasingly recognised in the pathogenesis of atherosclerosis and T2D, potentially forming an aetiological link between conditions. This link might reflect an overspill of inflammation from one affected organ into the systemic circulation, exposing all organs to an increased milieu of proinflammatory cytokines. Additionally, increasing evidence supports the involvement of other processes in chronic disease pathogenesis, such as cellular senescence or changes in cellular phenotypes.This review explores the current scientific evidence for inflammation, cellular ageing and cellular processes, such as reactive oxygen species production and phenotypic changes in the pathogenesis of COPD, T2D and atherosclerosis; highlighting common mechanisms shared across these diseases. We identify emerging therapeutic approaches that target these areas, but also where more work is still required to improve our understanding of the underlying cellular biology in a multimorbid disease setting.

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Section: Theme 1: Accelerated Ageing In Multimorbiditysupporting

confidence: 53%

Shared mechanisms of multimorbidity in COPD, atherosclerosis and type-2 diabetes: the neutrophil as a potential inflammatory target

2020

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“…13,14 The upregulation of miR-34a has been shown to promote cellular senescence in small airway fibroblasts of COPD patients. 15 Moreover, overexpression of miRNA-125a/b in COPD results in heightened airway inflammation by inducing A20, which mediates NF-κB activation, while inhibition of miRNA-125a/b decreases the induction of inflammatory cytokines. 16 Here, we provide evidence that miR-486-5p mediates the TLR4-triggered inflammatory response of alveolar macrophages in COPD.…”

Section: Introductionmentioning

confidence: 99%

<p>miRNA-486-5p Promotes COPD Progression by Targeting HAT1 to Regulate the TLR4-Triggered Inflammatory Response of Alveolar Macrophages</p>

Zhang¹,

Xu²,

Kong³

et al. 2020

COPD

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“…Research advances have demonstrated the crucial regulatory roles of miRNAs in many diseases, including COPD [13,14]. miR-34a was found to be up-regulated in small airway broblasts in COPD patients compared to non-smokers, and miR-34a could promote cellular senescence in small airway broblasts in COPD patients [15]. miRNA-125a/b overexpression in COPD resulted in heightened airway in ammation by inducing A20 which mediated NF-κB activation, while miRNA-125a/b inhibition decreased in ammatory cytokine induction [16].…”

Section: Introductionmentioning

confidence: 99%

miRNA-486-5p Promotes COPD Progression by Targeting HAT1 to Regulate the TLR4-Triggered Inflammatory Response of Alveolar Macrophages

Zhang

Kong

et al. 2020

Preprint

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Background: The aim of this study is to investigate the key regulatory miRNA-486-5p and underlying molecular mechanisms in chronic obstructive pulmonary disease (COPD) progression.Methods: Aberrant miRNA expression in smokers compared to non-smokers and COPD compared to normal was analyzed using microarray datasets and reverse-transcriptase quantitative polymerase chain reaction (qPCR). ELISA assay was used to determine the secretion of inflammatory cytokines in cell supernatants. Inflammatory cytokine expression, including HAT1, TLR4, and miR-486-5p, was determined using qPCR or western blotting. Luciferase reporter assays and fluorescence in situ hybridization were used to confirm the target regulation between miR-486-6p and HAT1. Results: Our results showed that miR-486-5p was significantly up-regulated in the COPD and smoker groups compared to the control group based on bioinformatics analysis and qPCR validation of alveolar macrophages and peripheral monocytes. miR-218-5p expression significantly correlated with IL-6, IL-8, TNF-α, and IFN-γ expression. Luciferase reporter assays confirmed that miR-486-5p directly targets HAT1, and cellular localization showed that miR-486-5p and HAT1 were highly expressed in the cytoplasm. miR-486-5p overexpression led to significant TLR4 up-regulation and significant HAT1 down-regulation. Inversely, miR-486-5p inhibition led to significant TLR4 down-regulation and significant HAT1 up-regulation. HAT1 knockdown using siRNA significantly increased TLR4, IL-6, IL-8, TNF-α, and IFN-γ expression. Conclusions: miR-486-5p was differentially expressed in alveolar macrophages of COPD patients. miR-486-5p overexpression might increase the TLR4-triggered inflammatory response in COPD patients by targeting HAT1.

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MicroRNA-34a drives small airway fibroblast cellular senescence in COPD

Cited by 3 publications

References 0 publications

Shared mechanisms of multimorbidity in COPD, atherosclerosis and type-2 diabetes: the neutrophil as a potential inflammatory target

Shared mechanisms of multimorbidity in COPD, atherosclerosis and type-2 diabetes: the neutrophil as a potential inflammatory target

<p>miRNA-486-5p Promotes COPD Progression by Targeting HAT1 to Regulate the TLR4-Triggered Inflammatory Response of Alveolar Macrophages</p>

miRNA-486-5p Promotes COPD Progression by Targeting HAT1 to Regulate the TLR4-Triggered Inflammatory Response of Alveolar Macrophages

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