Increased serum levels of lipocalin-1 and -2 in patients with stable chronic obstructive pulmonary disease

Wang, Xiaoru; Li, Yong-pu; Shui, Gao; Wei, Xia; Gao, Kun; Kong, Qing-hua; Qi, Hui; Wu, Ling; Zhang, Jing; Jian, Qu; Bai, Chunxue

doi:10.2147/copd.s62700

Cited by 23 publications

(20 citation statements)

References 27 publications

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“…In this study, we chose to measure urine extracellular urine mtDNA (u-mtDNA) levels, as it may serve as an indicator of systemic mitochondrial damage. Additionally, recent studies from our group and others provide evidence that individuals with COPD have a higher incidence of chronic kidney disease (CKD) (44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55) and that mitochondrial dysfunction may be one of the mechanisms behind this finding (56). Specifically, we have recently shown that exposure to cigarette smoke induces mitochondrial swelling and loss of cristae in murine renal tubular epithelial cells (56), and that glomerulosclerosis and tubulointerstitial fibrosis occur more frequently in patients with COPD than in control subjects (44).…”

Section: Introductionmentioning

confidence: 99%

Association of urine mitochondrial DNA with clinical measures of COPD in the SPIROMICS cohort

Zhang¹,

Rice²,

Hoffman³

et al. 2020

JCI Insight

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BACKGROUND. Mitochondrial dysfunction, a proposed mechanism of chronic obstructive pulmonary disease (COPD) pathogenesis, is associated with the leakage of mitochondrial DNA (mtDNA), which may be detected extracellularly in various bodily fluids. Despite evidence for the increased prevalence of chronic kidney disease in COPD subjects and for mitochondrial dysfunction in the kidneys of murine COPD models, whether urine mtDNA (u-mtDNA) associates with measures of disease severity in COPD is unknown. METHODS. Cell-free u-mtDNA, defined as copy number of mitochondrially encoded NADH dehydrogenase-1 (MTND1) gene, was measured by quantitative PCR and normalized to urine creatinine in cell-free urine samples from participants in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort. Urine albumin/creatinine ratios (UACR) were measured in the same samples. Associations between u-mtDNA, UACR, and clinical disease parameters-including FEV 1 % predicted, clinical measures of exercise tolerance, respiratory symptom burden, and chest CT measures of lung structure-were examined. RESULTS. U-mtDNA and UACR levels were measured in never smokers (n = 64), smokers without airflow obstruction (n = 109), participants with mild/moderate COPD (n = 142), and participants with severe COPD (n = 168). U-mtDNA was associated with increased respiratory symptom burden, especially among smokers without COPD. Significant sex differences in u-mtDNA levels were observed, with females having higher u-mtDNA levels across all study subgroups. U-mtDNA associated with worse spirometry and CT emphysema in males only and with worse respiratory symptoms in females only. Similar associations were not found with UACR.

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Section: Introductionmentioning

confidence: 99%

Association of urine mitochondrial DNA with clinical measures of COPD in the SPIROMICS cohort

Zhang¹,

Rice²,

Hoffman³

et al. 2020

JCI Insight

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“…A potential association between COPD and CKD prevalence has previously been suggested in several studies (6,12). COPD patients may exhibit an increased risk of lower estimated glomerular filtration rate (eGFR) (12), higher serum NGAL levels (57)(58)(59), and greater microalbuminuria (12,(60)(61)(62). Microalbuminuria has also been associated with a greater prevalence of hypoxemia (60), all-cause mortality (62), and acute exacerbations (63) in COPD patients.…”

Section: Discussionmentioning

confidence: 95%

Beclin-1 regulates cigarette smoke–induced kidney injury in a murine model of chronic obstructive pulmonary disease

Pabón¹,

Patiño²,

Bhatia³

et al. 2018

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Chronic obstructive pulmonary disease (COPD), associated with cigarette smoke-induced (CS-induced) emphysema, contributes significantly to the global health care burden of disease. Although chronic kidney disease (CKD) may occur in patients with COPD, the relationship between COPD and CKD remains unclear. Using a murine model of experimental COPD, we show that chronic CS exposure resulted in marked kidney injury and fibrosis, as evidenced by histological and ultrastructural changes, altered macrophage subpopulations, and expression of tissue injury, fibrosis, and oxidative stress markers. CS induced mitochondrial dysfunction, and increased autophagic flux in kidney tissues and in kidney tubular epithelial (HK-2) cells, as determined by LC3B turnover assays. Mice heterozygous for Beclin-1 (Becn1+/-) were protected from the development of kidney tissue injury and renal fibrosis in response to CS exposure, and displayed impaired basal and inducible mitochondrial turnover by mitophagy. Interestingly, CS caused a reduction of Beclin-1 expression in mouse kidneys and kidney tubular epithelial cells, attributed to increased autophagy-dependent turnover of Beclin-1. These results suggest that Beclin-1 is required for CS-induced kidney injury and that reduced levels of Beclin-1 may confer renoprotection. These results identify the kidney as a target for CS-induced injury in COPD and the Beclin-1-dependent autophagy pathway as a potential therapeutic target in CKD.

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“…LCN1 has previously been associated with respiratory diseases in humans, e.g. in COPD (chronic obstructive pulmonary disease) [35] and cystic fibrosis [36]. Animal lipocalins are known allergens promoting Th2 responses and inflammation [37].…”

Section: Discussionmentioning

confidence: 99%

Inhaled diesel exhaust alters the allergen-induced bronchial secretome in humans

et al. 2018

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Diesel exhaust (DE) is a paradigm for traffic-related air pollution. Human adaptation to DE is poorly understood and currently based on oversimplified models. DE promotes allergic responses, but protein expression changes mediated by this interaction have not been systematically investigated. The aim of this study was to define the effect of inhaled DE on allergen-induced proteins in the lung.We performed a randomised and blinded controlled human crossover exposure study. Participants inhaled filtered air or DE; thereafter, contralateral lung segments were challenged with allergen or saline. Using label-free quantitative proteomics, we comprehensively defined DE-mediated alteration of allergen-driven secreted proteins (secretome) in bronchoalveolar lavage. We further examined expression of proteins selected from the secretome data in independent validation experiments using Western blots, ELISA and immunohistochemistry.We identified protein changes unique to co-exposure (DE+allergen), undetected with mono-exposures (DE or allergen alone). Validation studies confirmed that specific proteins ( the antimicrobial peptide cystatin-SA) were significantly enhanced with DE+allergen compared to either mono-exposure.This study demonstrates that common environmental co-exposures can uniquely alter protein responses in the lungs, illuminating biology that mono-exposures cannot. This study highlights the value of complex human models in detailing airway responses to inhaled pollution.

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Increased serum levels of lipocalin-1 and -2 in patients with stable chronic obstructive pulmonary disease

Cited by 23 publications

References 27 publications

Association of urine mitochondrial DNA with clinical measures of COPD in the SPIROMICS cohort

Association of urine mitochondrial DNA with clinical measures of COPD in the SPIROMICS cohort

Beclin-1 regulates cigarette smoke–induced kidney injury in a murine model of chronic obstructive pulmonary disease

Inhaled diesel exhaust alters the allergen-induced bronchial secretome in humans

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