MicroRNA-125a and -b inhibit A20 and MAVS to promote inflammation and impair antiviral response in COPD

Hsu, Alan; Dua, Kamal; Starkey, Malcolm R.; Haw, Tatt Jhong; Nair, Prema M.; Nichol, Kristy S; Zammit, Nathan W.; Grey, Shane T.; Baines, Katherine J.; Foster, Paul S.; Hansbro, Philip M.; Wark, Peter

doi:10.1172/jci.insight.90443

Cited by 97 publications

(97 citation statements)

References 68 publications

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“…Furthermore, decreased expression of miR-125a and -b levels in COPD have been linked to inflammation and an impaired immune response. MiR-125a reduction resulted in NF-κB activation, with a classical induction of pro-inflammatory cytokines, while in parallel, low levels of miR-125a and -b suppress viral clearance [113]. These data underscore the potential of targeting inflammation and at the same time increasing resistance to infections in the aged individual with COPD.…”

Section: Cellular Processesmentioning

confidence: 74%

Lung ageing and COPD: is there a role for ageing in abnormal tissue repair?

et al. 2017

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Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide, with increasing prevalence, in particular in the elderly. COPD is characterised by abnormal tissue repair resulting in (small) airways disease and emphysema. There is accumulating evidence that ageing hallmarks are prominent features of COPD. These ageing hallmarks have been described in different subsets of COPD patients, in different lung compartments and also in a variety of cell types, and thus might contribute to different COPD phenotypes. A better understanding of the main differences and similarities between normal lung ageing and the pathology of COPD may improve our understanding of the mechanisms driving COPD pathology, in particular in those patients that develop the most severe form of COPD at a relatively young age, i.e. severe early-onset COPD patients.In this review, after introducing the main concepts of lung ageing and COPD pathology, we focus on the role of (abnormal) ageing in lung remodelling and repair in COPD. We discuss the current evidence for the involvement of ageing hallmarks in these pathological features of COPD. We also highlight potential novel treatment strategies and opportunities for future research based on our current knowledge of abnormal lung ageing in COPD.

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Section: Cellular Processesmentioning

confidence: 74%

Lung ageing and COPD: is there a role for ageing in abnormal tissue repair?

et al. 2017

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“…miR‐125a, a highly reserved miRNA locating on chromosome 19, 11, and 21, is also closely related to inflammation and immunity, and this miRNA has been reported to have the potential in regulating sepsis pathogenesis . Moreover, it is a direct target of lnc‐ANRIL, and the lnc‐ANRIL/miR‐125a axis has been indicated in many diseases . However, the role of lnc‐ANRIL/miR‐125a axis in sepsis remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Elevated circulating lnc‐ANRIL/miR‐125a axis level predicts higher risk, more severe disease condition, and worse prognosis of sepsis

Gui

Peng

Liu

2019

Clinical Laboratory Analysis

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Aim This study aimed to investigate the correlation of lnc‐ANRIL/miR‐125a axis with risk, severity, inflammation, and prognosis of sepsis. Methods A hundred and twenty‐six sepsis patients and 125 healthy controls were recruited, and then, blood samples were collected, and plasma was separated for lnc‐ANRIL, miR‐125a, lnc‐ANRIL/miR‐125a axis, and inflammatory cytokine level detections. In addition, basic characteristics, 28‐day mortality, and accumulating survival of sepsis patients were recorded. Results Plasma lnc‐ANRIL expression was increased, miR‐125a expression was decreased, and lnc‐ANRIL/miR‐125a axis level was elevated in sepsis patients compared with healthy controls, and all of them had good value for predicting sepsis risk with AUCs of 0.800, 0.817, and 0.843, respectively. Lnc‐ANRIL and lnc‐ANRIL/miR‐125a axis were positively correlated with biochemical index levels including CRP and PCT levels, disease severity scale scores, and pro‐inflammatory cytokine levels in sepsis patients, while miR‐125a displayed the opposite trend. Lnc‐ANRIL and lnc‐ANRIL/miR‐125a axis expressions were elevated, while miR‐125a expression was declined in deaths compared with survivors, and all of them predicted 28‐day mortality in sepsis patients with AUCs of 0.765, 0.745, and 0.785, respectively. Subsequently, the Kaplan‐Meier analysis revealed that patients with high lnc‐ANRIL, low miR‐125a, and high lnc‐ANRIL/miR‐125a axis levels presented with worse accumulating survival. In addition, multivariate regression model analyses revealed that high plasma lnc‐ANRIL/miR‐125a axis was an independent predictive factor for both increased 28‐day mortality and worse accumulating survival. Conclusion Circulating lnc‐ANRIL/miR‐125a axis was upregulated and could serve as a biomarker for severity, inflammation, and prognosis in sepsis patients.

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“…NF‐κB is also regulated by PHD (primarily PHD1), which reveals a common molecular pathway connecting hypoxia‐dependent regulation of HIF‐1 and NF‐κB . However, it remains unclear when CS‐induced HIF‐1α activation/overexpression and related pathology become important in the human disease course, which needs further investigation in experimental mouse models that recapitulate human disease features, and confirmed in prospective human studies …”

Section: Hypoxaemia and Hypoxia In Copdmentioning

confidence: 99%

“…The role of HIF‐1α‐induced PAFR expression as a driver of bacterial infection has not been widely studied in the lungs . Advances in developing representative murine models of human COPD have occurred in the past decade that is enabling us to elucidate the mechanisms involved in HIF‐1α‐induced, PAFR‐mediated bacterial infections in AECOPD …”

Section: Hif‐1α‐induced Pafr‐mediated Bacterial Infections In Copdmentioning

confidence: 99%

Hypoxia‐inducible factor and bacterial infections in chronic obstructive pulmonary disease

et al. 2019

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COPD is a seriously disabling respiratory condition that inexorably progresses to disability and mortality. It affects approximately 10% of the population globally with a greater prevalence at advanced ages. Airway bacterial infections complicate the disease course in most COPD patients, leading to increased symptoms, more rapid decline in lung function, acute exacerbations and reduced quality of life. With increasing bacterial resistance to antibiotics and adverse effects of conventional treatments, new effective non‐antibiotic antimicrobial therapies are urgently needed to manage COPD. Hypoxia‐inducible factor (HIF)‐1α is an important transcriptional regulator of cellular responses to hypoxia, oxidants and inflammation, and is overexpressed in the lungs of COPD patients. Recent evidence shows that increased HIF‐1α expression can upregulate the platelet‐activating factor receptor (PAFR) on the airway epithelial surface that is increased in smokers and particularly COPD patients. The receptor is utilized by PAFR‐dependent bacteria (Streptococcus pneumoniae, Haemophilus influenzae and Pseudomonas aeruginosa) to induce infection in both the respiratory and gastrointestinal (GI) tracts. However, the importance and mechanism of HIF‐1α in augmenting PAFR‐dependent bacterial infections in COPD are poorly understood. Here, we review the evidence for the roles of local tissue hypoxia‐induced inflammation, HIF‐1α and PAFR in facilitating bacterial infections in COPD. Blocking PAFR may provide a novel antimicrobial approach to manage bacterial infections in COPD.

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MicroRNA-125a and -b inhibit A20 and MAVS to promote inflammation and impair antiviral response in COPD

Cited by 97 publications

References 68 publications

Lung ageing and COPD: is there a role for ageing in abnormal tissue repair?

Lung ageing and COPD: is there a role for ageing in abnormal tissue repair?

Elevated circulating lnc‐ANRIL/miR‐125a axis level predicts higher risk, more severe disease condition, and worse prognosis of sepsis

Hypoxia‐inducible factor and bacterial infections in chronic obstructive pulmonary disease

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