BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive, eventually fatal disease. IPF is characterized by excessive accumulation of the extracellular matrix (ECM) in the alveolar parenchyma and progressive lung scarring. The pathogenesis of IPF and whether the ECM involved in the process remain unknown.MethodsTo identify potential treatment target and ECM associated proteins that may be involved in the development of IPF, we employed isobaric tag for relative and absolute quantitation (iTRAQ) combined liquid chromatography–tandem mass spectrometry (LC–MS/MS) approach to examine protein expression in lung tissues from IPF patients.ResultsA total of 662 proteins with altered expression (455 upregulated proteins and 207 downregulated proteins) were identified in lung tissue of IPF patients compared with control. KEGG pathway enrichment analysis showed that the altered proteins in lung tissue mainly belonged to the PI3K-Akt signaling, focal adhesion, ECM-receptor interaction, and carbon metabolism pathways. According to the bioinformatic definition of the matrisome, 229 matrisome proteins were identified in lung tissue. These proteins comprised the ECM of lung, of which 104 were core matrisome proteins, and 125 were matrisome-associated proteins. Of the 229 ECM quantified proteins, 56 significantly differentially expressed proteins (19 upregulated proteins and 37 downregulated proteins) were detected in IPF lung tissue samples. In addition to proteins with well-known functions such as COL1A1, SCGB1A1, TAGLN, PSEN2, TSPAN1, CTSB, AGR2, CSPG2, and SERPINB3, we identified several novel ECM proteins with unknown function deposited in IPF lung tissue including LGALS7, ASPN, HSP90AA1 and HSP90AB1. Some of these differentially expressed proteins were further verified using Western blot analysis and immunohistochemical staining.ConclusionsThis study provides a list of proteomes that were detected in IPF lung tissue by iTRAQ technology combined with LC–MS/MS. The findings of this study will contribute better understanding to the pathogenesis of IPF and facilitate the development of therapeutic targets.Electronic supplementary materialThe online version of this article (10.1186/s12014-019-9226-4) contains supplementary material, which is available to authorized users.
Purpose. This study aims at investigating the predictive value of red blood cell distribution width (RDW) in pulmonary hypertension (PH) secondary to chronic obstructive pulmonary disease (COPD). Methods. 213 eligible in-hospital COPD patients were reviewed between May 2016 and May 2018, including 39 cases with PH and 174 without PH. Clinical data including demographic characteristics, comorbidities, and results of ultrasound scans, imaging examinations, and laboratory tests were recorded. Results. Increased RDW level was observed in COPD patients with PH compared with COPD patients without PH, with 15.10 ± 1.72% versus 13.70 ± 1.03%, respectively (p<0.001). RDW shared positive relationships with brain natriuretic peptide (BNP) (p=0.001, r = 0.513), pulmonary artery (PA) systolic pressure (p=0.014, r = 0.390), and PA-to-ascending aorta (A) ratio (PA : A) (p=0.001, r = 0.502). Multivariate analysis indicated that RDW, BNP, and PA : A > 1 were the independent risk factors of PH secondary to COPD (p<0.05). The AUC of the RDW in patients with PH was 0.749 ± 0.054 (p<0.001). The optimal cutoff value of RDW for predicting PH was 14.65, with a sensitivity and a specificity value of 69.2% and 82.8%, respectively. Conclusion. RDW is significantly increased in COPD patients with PH and thus may be a useful biomarker for PH secondary to COPD.
Background. Connective tissue disease (CTD) associated with interstitial lung disease (ILD) affects the lungs and can lead to considerable morbidity and shortened survival. Red blood cell distribution width (RDW) is a readily available parameter that is routinely reported with complete blood cell count (CBC) This study aimed to investigate the predictive value of RDW in CTD-ILD. Methods. A retrospective analysis was performed on 180 patients with CTD-ILD and 202 patients with CTD but without ILD between April 2016 and December 2018. Baseline demographics, laboratory results, imaging examinations, and results of ultrasound scans were analysed. Results. In comparison with patients without ILD, patients with CTD-ILD displayed a larger RDW (14.65 ± 2.08 vs. 14.17 ± 1.63, P=0.002), and RDW shared positive relationships with pulmonary artery systolic pressure (r = 0.349; P<0.001), length of hospital confinement (r = 0.172; P=0.022), and hospitalisation expenses (r = 0.158; P=0.037). Multivariate logistic regression analysis showed that RDW (odds ratio (OR): 1.232, 95% confidence interval (CI): 1.053–1.422, P=0.009), IgG (OR: 1.103, 95% CI: 1.051–1.159, P<0.001), and age (OR: 1.032, 95% CI: 1.010–1.054, P=0.004) are independent predictors of CTD-ILD risk. The optimal cut-off value of RDW for predicting CTD-ILD was 14.85%, with a sensitivity and a specificity value of 41.2% and 75.2%, respectively. Conclusions. RDW was significantly increased in patients with CTD-ILD under various CTD backgrounds and may be a promising biomarker that may help physicians predict CTD-ILD risk.
Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease. COPD is associated with accelerated lung aging. Circadian clock is believed to play important roles in COPD. Although the circadian molecular clock regulates cellular senescence, there is no information available regarding the impact of COPD. The aim of this study is to investigate the role of the circadian clock protein BMAL1 and CLOCK in cellular senescence in order to understand the cellular mechanisms of accelerated aging of COPD. Bmal1 and Clock levels were assessed in the plasma samples of non-smokers, smokers, and patients with COPD. The regulation of ciracadian clock expression and cell senescence by cigarette smoke extract (CSE) was studied in vitro, and small interfering RNA (siRNA) and overexpression of Bmal1 or Clock were employed to investigate the role of circadian clock on cell senescence. Herein, patients with COPD showed lower Bmal1 and Clock expression in the plasma. Interestingly, CSE exposure contributed to the increased cell senescence, decreased Clock and Bmal1 in human bronchial epithelial cells (Beas-2B cells). We found that knockdown of Clock or Bmal1 lead to upregulation of cell senescence in Beas-2B cells, while overexpression of Clock or Bmal1 inhibited cell senescence in Beas-2B cells, which is through the MAPK pathways. Therefore, our findings indicated that Bmal1 or Clock deficiency may be a significant factor to increase cellular senescence of the lung to develop COPD.
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