scholarly journals CUL1-Mediated Organelle Fission Pathway Inhibits the Development of Chronic Obstructive Pulmonary Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Ran Li ◽  
Feng Xu ◽  
Xiao Wu ◽  
Shaoping Ji ◽  
Ruixue Xia
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Transcription Factors ◽  
Pulmonary Disease ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Development Trend ◽  
Chronic Obstructive ◽  
Hypergeometric Test ◽  
Obstructive Pulmonary Disease ◽  
Depth Analysis

Chronic obstructive pulmonary disease (COPD) is a global high-incidence chronic airway inflammation disease. Its deterioration will lead to more serious lung lesions and even lung cancer. Therefore, it is urgent to determine the pathogenesis of COPD and find potential therapeutic targets. The purpose of this study is to reveal the molecular mechanism of COPD disease development through in-depth analysis of transcription factors and ncRNA-driven pathogenic modules of COPD. We obtained the expression profile of COPD-related microRNAs from the NCBI-GEO database and analyzed the differences among groups to identify the microRNAs significantly associated with COPD. Then, their target genes are predicted and mapped to a protein-protein interaction (PPI) network. Finally, key transcription factors and the ncRNA of the regulatory module were identified based on the hypergeometric test. The results showed that CUL1 was the most interactive gene in the highly interactive module, so it was recognized as a dysfunctional molecule of COPD. Enrichment analysis also showed that it was much involved in the biological process of organelle fission, the highest number of regulatory modules. In addition, ncRNAs, mainly composed of miR-590-3p, miR-495-3p, miR-186-5p, and transcription factors such as MYC, BRCA1, and CDX2, significantly regulate COPD dysfunction blocks. In summary, we revealed that the COPD-related target gene CUL1 plays a key role in the potential dysfunction of the disease. It promotes the proliferation of fibroblast cells in COPD patients by mediating functional signals of organelle fission and thus participates in the progress of the disease. Our research helps biologists to further understand the etiology and development trend of COPD.

scholarly journals GPNMB contributes to a vicious circle for chronic obstructive pulmonary disease

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Xi-Juan Zhang ◽  
Zhong-Hua Cui ◽  
Yan Dong ◽  
Xiu-Wen Liang ◽  
Yan-Xin Zhao ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Large Scale ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Chronic Obstructive ◽  
P Value ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Size Population

Abstract Osteoporosis (OP) is significant and debilitating comorbidity of chronic obstructive pulmonary disease (COPD). We hypothesize that genetic variance identified with OP may also play roles in COPD. We have conducted a large-scale relation data analysis to explore the genes implicated with either OP or COPD, or both. Each gene linked to OP but not to COPD was further explored in a mega-analysis and partial mega-analysis of 15 independently collected COPD RNA expression datasets, followed by gene set enrichment analysis (GSEA) and literature-based pathway analysis to explore their functional linked to COPD. A multiple linear regression (MLR) model was built to study the possible influence of sample size, population region, and study date on the gene expression data in COPD. At the first step of the analysis, we have identified 918 genes associated with COPD, 581 with OP, and a significant overlap (P<2.30e-140; 210 overlapped genes). Partial mega-analysis showed that, one OP gene, GPNMB presented significantly increased expression in COPD patients (P-value = 0.0018; log fold change = 0.83). GPNMB was enriched in multiple COPD pathways and plays roles as a gene hub formulating multiple vicious COPD pathways included gene MMP9 and MYC. GPNMB could be a novel gene that plays roles in both COPD and OP. Partial mega-analysis is valuable in identify case-specific genes for COPD.

scholarly journals Transcription factors involved in stem cell maintenance are downstream of Slug/Snail2 and repressed by TGF-β in bronchial epithelial progenitors from Chronic Obstructive Pulmonary Disease

2019 ◽  
Author(s):  
Pierre de la Grange ◽  
Ariane Jolly ◽  
Charlotte Courageux ◽  
Chamseddine Ben Brahim ◽  
Pascale LEROY
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Stem Cell ◽  
Transcription Factors ◽  
Pulmonary Disease ◽  
Chronic Obstructive ◽  
Mrna Levels ◽  
Differentiation Potential ◽  
Obstructive Pulmonary Disease ◽  
Stem Cell Maintenance ◽  
Cell Maintenance

Abstract Objectives: Patients with Chronic Obstructive Pulmonary Disease (COPD) have a bronchial epithelium with many anomalies and basal/progenitor cells showing a decrease of self-renewal and differentiation potential. The objective of this study was to identify deregulations in the genetic program of COPD bronchial progenitors that could account for their exhaustion. The transcription factor Slug/Snail2 is highly expressed in bronchial progenitors and we aimed at identifying genes downstream of Slug whose expression is deregulated in COPD progenitors. Results: We knocked down Slug in primary basal cells from COPD subjects and, since COPD subjects have higher levels of Transforming Growth Factor (TGF)-β Slug is regulated by TGF-β, we selected genes downstream of Slug involved in differentiation that respond to TGF-β. We identified transcription factors involved in stem cell maintenance downstream of Slug and repressed by TGF-β in COPD but not normal progenitors. We found that the effect of TGF-β on the expression of these genes is correlated to Slug knockdown effect. We also found a correlation between the mRNA levels of Slug and these genes only in presence of TGF-β. These results reveal that stem cell maintenance genes are deregulated in COPD bronchial progenitors, Slug and TGF-β being involved in that deregulation.

scholarly journals Suppressed Expression of T-Box Transcription Factors Is Involved in Senescence in Chronic Obstructive Pulmonary Disease

2012 ◽  
Vol 8 (7) ◽  
pp. e1002597 ◽  
Author(s):  
George K. Acquaah-Mensah ◽  
Deepti Malhotra ◽  
Madhulika Vulimiri ◽  
Jason E. McDermott ◽  
Shyam Biswal
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Transcription Factors ◽  
Pulmonary Disease ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
T Box

scholarly journals Determining Pharmacological Mechanisms of Chinese Incompatible Herbs Fuzi and Banxia in Chronic Obstructive Pulmonary Disease: A Systems Pharmacology-Based Study

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Kaiwen Ni ◽  
Xiaolu Cai ◽  
Yaling Chen ◽  
Linshui Zhou ◽  
Ruilin Chen ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Target Genes ◽  
Network Pharmacology ◽  
Chronic Obstructive ◽  
Healthy Individuals ◽  
Obstructive Pulmonary Disease ◽  
Pathway Network ◽  
Gene Pathway ◽  
Copd Patients

Aconiti Lateralis Radix Praeparata (Fuzi) and Pinelliae Rhizoma (Banxia) are among the 18 incompatible medications that are forbidden from use in one formulation. However, there is increasing evidence implying that this prohibition is not entirely correct. According to the theory of Chinese traditional medicine, they can be used for the treatment of chronic obstructive pulmonary disease (COPD). Thus, we analyzed the possible approaches for the treatment of COPD using network pharmacology. The active compounds of Fuzi and Banxia (FB) were collected, and their targets were identified. COPD-related targets were obtained by analyzing the differentially expressed genes between COPD patients and healthy individuals, which were expressed using a Venn diagram of COPD and FB. Protein-protein interaction data and network regarding COPD and drugs used were obtained. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted. The gene-pathway network was constructed to screen the key target genes. In total, 34 active compounds and 47 targets of FB were identified; moreover, 7,153 differentially expressed genes were identified between COPD patients and healthy individuals. The functional annotations of target genes were found to be related to mechanisms such as transcription, cytosol, and protein binding; furthermore, 68 pathways including neuroactive ligand-receptor interaction, Kaposi sarcoma-associated herpesvirus infection, apoptosis, and measles were significantly enriched. FOS CASP3, VEGFA, ESR1, and PTGS2 were the core genes in the gene-pathway network of FB for the treatment of COPD. Our results indicated that the effect of FB against COPD may involve the regulation of immunological function through several specific biological processes and their corresponding pathways. This study demonstrates the application of network pharmacology in evaluating mechanisms of action and molecular targets of herb-opponents FB.

Oral and Oropharyngeal Sensory Function in Adults With Chronic Obstructive Pulmonary Disease

2020 ◽  
Vol 29 (2) ◽  
pp. 864-872
Author(s):  
Fernanda Borowsky da Rosa ◽  
Adriane Schmidt Pasqualoto ◽  
Catriona M. Steele ◽  
Renata Mancopes
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Oral Cavity ◽  
Pulmonary Disease ◽  
Thermal Sensation ◽  
Sensory Function ◽  
Control Group ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Age Related ◽  
Copd Patients

Introduction The oral cavity and pharynx have a rich sensory system composed of specialized receptors. The integrity of oropharyngeal sensation is thought to be fundamental for safe and efficient swallowing. Chronic obstructive pulmonary disease (COPD) patients are at risk for oropharyngeal sensory impairment due to frequent use of inhaled medications and comorbidities including gastroesophageal reflux disease. Objective This study aimed to describe and compare oral and oropharyngeal sensory function measured using noninstrumental clinical methods in adults with COPD and healthy controls. Method Participants included 27 adults (18 men, nine women) with a diagnosis of COPD and a mean age of 66.56 years ( SD = 8.68). The control group comprised 11 healthy adults (five men, six women) with a mean age of 60.09 years ( SD = 11.57). Spirometry measures confirmed reduced functional expiratory volumes (% predicted) in the COPD patients compared to the control participants. All participants completed a case history interview and underwent clinical evaluation of oral and oropharyngeal sensation by a speech-language pathologist. The sensory evaluation explored the detection of tactile and temperature stimuli delivered by cotton swab to six locations in the oral cavity and two in the oropharynx as well as identification of the taste of stimuli administered in 5-ml boluses to the mouth. Analyses explored the frequencies of accurate responses regarding stimulus location, temperature and taste between groups, and between age groups (“≤ 65 years” and “> 65 years”) within the COPD cohort. Results We found significantly higher frequencies of reported use of inhaled medications ( p < .001) and xerostomia ( p = .003) in the COPD cohort. Oral cavity thermal sensation ( p = .009) was reduced in the COPD participants, and a significant age-related decline in gustatory sensation was found in the COPD group ( p = .018). Conclusion This study found that most of the measures of oral and oropharyngeal sensation remained intact in the COPD group. Oral thermal sensation was impaired in individuals with COPD, and reduced gustatory sensation was observed in the older COPD participants. Possible links between these results and the use of inhaled medication by individuals with COPD are discussed.

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