Chronic exposure to ambient particulate matter induces gut microbial dysbiosis in a rat COPD model.

BACKGROUND: The role of the microbiota in the pathogenesis of chronic obstructive pulmonary disease (COPD) following exposure to ambient particulate matter (PM) is largely unknown. METHODS: Fifty-four male Sprague-Dawley rats were exposed to clean air, biomass fuel (BMF), or motor vehicle exhaust (MVE) for 4, 12, and 24 weeks. We performed pulmonary inflammation evaluation, morphometric measurements, and lung function analysis in rat lung at three different times points during exposure. Lung and gut microbial composition was assessed by 16S rRNA pyrosequencing. Serum lipopolysaccharide levels were measured and short-chain fatty acids in colon contents were quantified. RESULTS: After a 24-week PM exposure, rats exhibited pulmonary inflammation and pathological changes characteristic of COPD. The control and PM exposure (BMF and MVE) groups showed similar microbial diversity and composition in rat lung. However, the gut microbiota after 24 weeks PM exposure was characterized by decreased microbial richness and diversity, distinct overall microbial composition, lower levels of short-chain fatty acids, and higher serum lipopolysaccharide. CONCLUSION: Chronic exposure to ambient particulate matter induces gut microbial dysbiosis and metabolite shifts in a rat model of chronic obstructive pulmonary disease.

Development of a transcriptomic database for 14 species of scleractinian corals.

BACKGROUND: Scleractinian corals are important reef builders, but around the world they are under the threat of global climate change as well as local stressors. Molecular resources are critical for understanding a species' stress responses and resilience to the changing environment, but such resources are unavailable for most scleractinian corals, especially those distributed in the South China Sea. We therefore aimed to provide transcriptome resources for 14 common species, including a few structure forming species, in the South China Sea. DESCRIPTION: We sequenced the transcriptome of 14 species of scleractinian corals using high-throughput RNA-seq and conducted de novo assembly. For each species, we produced 7.4 to 12.0 gigabases of reads, and assembled them into 271 to 762 thousand contigs with a N50 value of 629 to 1427 bp. These contigs included 66 to 114 thousand unigenes with a predicted open reading frame, and 74.3 to 80.5% of the unigenes were functionally annotated. In the azooxanthelate species Tubastraea coccinea, 41.5% of the unigenes had at least a best-hit sequence from corals. In the other thirteen species, 20.2 to 48.9% of the annotated unigenes had best-hit sequences from corals, and 28.3 to 51.6% from symbiotic algae belonging to the family Symbiodinaceae. With these resources, we developed a transcriptome database (CoralTBase) which features online BLAST and keyword search for unigenes/functional terms through a user friendly Internet interface. SHORT CONCLUSION: We developed comprehensive transcriptome resources for 14 species of scleractinian corals and constructed a publicly accessible database ( www.comp.hkbu.edu.hk/~db/CoralTBase ). CoralTBase will facilitate not only functional studies using these corals to understand the molecular basis of stress responses and adaptation, but also comparative transcriptomic studies with other species of corals and more distantly related cnidarians.

Long Noncoding RNA COPDA1 Promotes Airway Smooth Muscle Cell Proliferation in Chronic Obstructive Pulmonary Disease.

Abnormal expression of long noncoding RNAs (lncRNAs) has been confirmed to be associated with many diseases, including chronic obstructive pulmonary disease (COPD). To gain better understanding of the mechanism of COPD, we investigated the lncRNA and mRNA profiles in the lung tissue of patients with COPD. According to the analysis, one of the significantly different lncRNAs, COPDA1, might participate in the occurrence and development of COPD. Lung tissues were collected from nonsmokers, smokers, or smokers with COPD for RNA sequencing. Bioinformatic analysis and cell experiments were used to define the function of COPDA1, and the effects of COPDA1 on intracellular Ca2+ concentration and cell proliferation were examined after knockdown or overexpression of COPDA1. A number of variations of lncRNAs were found in the comparison of nonsmokers, smokers, and smokers with COPD. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses indicated that smoking was involved in the activation of cytokines and the cell cycle, which is associated with COPD. According to the lncRNA-mRNA-coexpressing network and enrichment analysis, COPDAz1 and one of its target genes, MS4A1 (membrane-spanning 4-domains family, subfamily A) were investigated, and we discovered that the expression of MS4A1 was closely associated with lncRNA COPDA1 expression in human bronchial smooth muscle cells (HBSMCs). Further study showed that lncRNA COPDA1 upregulated the expression of MS4A1 to increase store-operated calcium entry in the HBSMCs, resulting in the promotion of the proliferation of smooth muscle cells as well as of airway remodeling. COPDA1 might be involved in the regulation of certain signaling pathways in COPD, might promote the proliferation of HBSMCs, and might also be involved in facilitating airway remodeling.

Positive feedback of the amphiregulin-EGFR-ERK pathway mediates PM2.5 from wood smoke-induced MUC5AC expression in epithelial cells.

Biomass fuel smoke is thought to contribute to chronic obstructive pulmonary disease, which is characterized by mucous cell metaplasia and enhanced mucus secretion. We investigated the effect of particulate matter (PM) with a diameter <2.5 µm (PM2.5) from wood smoke (WSPM2.5) on the expression of the most prominent secreted mucin, MUC5AC. Wood smoke was able to induce MUC5AC expression in the rat respiratory tract after 3 months of exposure. WSPM2.5 could induce MUC5AC production in both primary human airway epithelial cells and the NCI-H292 cell line. This induction process was mediated by activation of epithelial growth factor receptor (EGFR)-extracellular signal-regulated kinase (ERK) signaling through an EGFR ligand-dependent mechanism. Amphiregulin (AR) was identified as the major ligand responsible for EGFR-ERK signaling activation and MUC5AC expression. In turn, EGFR-ERK pathway activation was found to contribute to the de novo synthesis of AR. This positive feedback loop might play an important role in a sustained mucus hypersecretion response.

Nicotine-Induced Airway Smooth Muscle Cell Proliferation Involves TRPC6-Dependent Calcium Influx Via α7 nAChR.

BACKGROUND/AIMS: The proliferation of human bronchial smooth muscle cells (HBSMCs) is a key pathophysiological component of airway remodeling in chronic obstructive pulmonary disease (COPD) for which pharmacotherapy is limited, and only slight improvements in survival have been achieved in recent decades. Cigarette smoke is a well-recognized risk factor for COPD; however, the pathogenesis of cigarette smoke-induced COPD remains incompletely understood. This study aimed to investigate the mechanisms by which nicotine affects HBSMC proliferation. METHODS: Cell viability was assessed with a CCK-8 assay. Proliferation was measured by cell counting and EdU immunostaining. Fluorescence calcium imaging was performed to measure intracellular Ca2+ concentration ([Ca2+]i). RESULTS: The results showed that nicotine promotes HBSMC proliferation, which is accompanied by elevated store-operated calcium entry (SOCE), receptor-operated calcium entry (ROCE) and basal [Ca2+]i in HBSMCs. Moreover, we also confirmed that canonical transient receptor potential protein 6 (TRPC6) and α7 nicotinic acetylcholine receptor (α7 nAChR) are involved in nicotine-induced upregulation of cell proliferation. Furthermore, we verified that activation of the PI3K/Akt signaling pathway plays a pivotal role in nicotine-enhanced proliferation and calcium influx in HBSMCs. Inhibition of α7 nAChR significantly decreased Akt phosphorylation levels, and LY294002 inhibited the protein expression levels of TRPC6. CONCLUSION: Herein, these data provide compelling evidence that calcium entry via the α7 nAChR-PI3K/Akt-TRPC6 signaling pathway plays an important role in the physiological regulation of airway smooth muscle cell proliferation, representing an important target for augmenting airway remodeling.

Exposure to ambient particulate matter alters the microbial composition and induces immune changes in rat lung.

BACKGROUND: Ambient particulate matter exposure has been shown to increase the risks of respiratory diseases. However, the role of the lung microbiome and the immune response to inhaled particulate matter are largely unexplored. We studied the influence of biomass fuel and motor vehicle exhaust particles on the lung microbiome and pulmonary immunologic homeostasis in rats. METHODS: Fifty-seven Sprague-Dawley rats were randomly divided into clean air (CON), biomass fuel (BMF), and motor vehicle exhaust (MVE) groups. After a 4-week exposure, the microbial composition of the lung was assessed by 16S rRNA pyrosequencing, the structure of the lung tissue was assessed with histological analysis, the phagocytic response of alveolar macrophages to bacteria was determined by flow cytometry, and immunoglobulin concentrations were measured with commercial ELISA kits. RESULTS: There was no significant difference in lung morphology between the groups. However, the BMF and MVE groups displayed greater bacterial abundance and diversity. Proteobacteria were present in higher proportions in the MVE group, and 12 bacterial families differed in their relative abundances between the three groups. In addition, particulate matter exposure significantly increased the capacity of alveolar macrophages to phagocytose bacteria and induced changes in immunoglobulin levels. CONCLUSION: We demonstrated that particulate matter exposure can alter the microbial composition and change the pulmonary immunologic homeostasis in the rat lung.

Exposure to Ambient Particulate Matter Induced COPD in a Rat Model and a Description of the Underlying Mechanism.

While the health effects of air pollution have been an international public health concern since at least the 1950s, recent research has focused on two broad sources of air pollution, namely, biomass fuel (BMF) and motor vehicle exhaust (MVE). Many studies have shown associations between air pollution PM and exacerbations of pre-existing COPD, but the role of air pollution PM in the development and progression of COPD is still uncertain. The current study indicates that rats can develop pronounced COPD following chronic exposure to air pollution PM (BMF and MVE), as characterized by lung function reduction, mucus metaplasia, lung and systemic inflammation, emphysema, and small airway remodeling. Comparative analyses demonstrate that both BMF and MVE activate similar pathogenesis that are linked to the development of COPD. These findings also show that some differences are found in the lungs of rats exposed to BMF or MVE, which might result in different phenotypes of COPD.