scholarly journals Comparative RNA-Seq Transcriptome Analysis on Pulmonary Inflammation in a Mouse Model of Asthma–COPD Overlap Syndrome

2021 ◽  
Vol 9 ◽  
Author(s):  
Pei Ma ◽  
Shuyi Li ◽  
Hui Yang ◽  
Jiqiao Yuan ◽  
Ziqian Zhang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Molecular Mechanisms ◽  
Pulmonary Inflammation ◽  
Clinical Syndrome ◽  
Overlap Syndrome ◽  
Mouse Lung ◽  
Control Group ◽  
Chronic Obstructive ◽  
Rna Seq ◽  
Immune System Activation

Asthma–chronic obstructive pulmonary disease (COPD) overlap (ACO) is a severe clinical syndrome characterized to describe patients with both asthma and COPD clinical characteristics, which has posed a serious threat to patients’ quality of life and life safety. However, there are many difficulties and uncertainties in its diagnosis and treatment in clinic; especially, its animal model has not been fully and thoroughly established, and the evaluation of therapeutic drugs is still in its infancy. Here, we used ovalbumin (OVA), lipopolysaccharide (LPS), and smoke costimulation to establish an ACO mouse model and then used RNA-seq technology to detect gene expression in mouse lung tissue. The results showed that ACO mice showed an overlap syndrome of asthma and COPD in lung histological changes and the levels of inflammatory cytokines in bronchoalveolar lavage fluid. The RNA-seq analysis results showed that 6,324 differentially expressed genes (DEGs) were screened between the ACO group and the control group, of which 2,717 (42.7%) were downregulated, and 3,607 (57.3%) were upregulated. Metascape analysis results showed that in the ACO model we established, due to the damage of the respiratory system, the accumulated diseased tissue involves lung, spleen, blood, bone marrow, thymus, etc. It has certain characteristics of pneumonia, pulmonary fibrosis, and chronic obstructive airway disease, lung tumors, rheumatoid arthritis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed that DEGs were enriched in inflammation, immune system activation and imbalance, cell proliferation, and adhesion migration, and the upstream signaling pathways of inflammation were mainly affected by HLA-DRA, SYK, CTLA4, VAV1, NRAS, and JAK3. In short, our research established a mouse model that can better simulate the clinicopathological characteristics of ACO and suggested the foundations in elucidating the molecular mechanisms for pulmonary inflammation and fibrosis in ACO. This work may help further research and contribute substantially to prevention and clinical treatment of ACO in the future.

scholarly journals Effect of Slit/Robo signaling on regeneration in lung emphysema

2021 ◽  
Author(s):  
Jin-Soo Park ◽  
RyeonJin Cho ◽  
Eun-Young Kang ◽  
Yeon-Mok Oh
Keyword(s):  
Epithelial Cells ◽  
Mouse Model ◽  
Lung Epithelial Cells ◽  
Mouse Lung ◽  
Chronic Obstructive ◽  
Irreversible Damage ◽  
Lung Epithelial ◽  
And Migration ◽  
Proliferation And Migration

AbstractEmphysema, a pathological component of chronic obstructive pulmonary disease, causes irreversible damage to the lung. Previous studies have shown that Slit plays essential roles in cell proliferation, angiogenesis, and organ development. In this study, we evaluated the effect of Slit2 on the proliferation and migration of mouse lung epithelial cells and its role in regeneration in an emphysema lung mouse model. Here, we have shown that Slit2/Robo signaling contributes to the regeneration of lungs damaged by emphysema. Mouse epithelial lung cells treated with Slit2 exhibited increased proliferation and migration in vitro. Our results also showed that Slit2 administration improved alveolar regeneration in the emphysema mouse model in vivo. Furthermore, Slit2/Robo signaling increased the phosphorylation of ERK and Akt, which was mediated by Ras activity. These Slit2-mediated cellular signaling processes may be involved in the proliferation and migration of mouse lung epithelial cells and are also associated with the potential mechanism of lung regeneration. Our findings suggest that Slit2 administration may be beneficial for alveolar regeneration in lungs damaged by emphysema.

scholarly journals Maternal factor PABPN1L is essential for maternal mRNA degradation during maternal-to-zygotic transition

2020 ◽  
Author(s):  
Ying Wang ◽  
Tianhao Feng ◽  
Xiaodan Shi ◽  
Siyu Liu ◽  
Zerui Wang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Large Scale ◽  
Mrna Degradation ◽  
Female Infertility ◽  
Control Group ◽  
Rna Seq ◽  
Cell Stage ◽  
Maternal Mrna ◽  
Maternal To Zygotic Transition ◽  
Group A

AbstractInfertility affects 10% - 15% of families worldwide. However, the pathogenesis of female infertility caused by abnormal early embryonic development is not clear. We constructed a mouse model (Pabpn1l -/-) simulating the splicing abnormality of human PABPN1L and found that the female was sterile and the male was fertile. The Pabpn1l -/- oocytes can be produced, ovulated and fertilized normally, but cannot develop beyond the 2-cell stage. Using RNA-Seq, we found a large-scale upregulation of RNA in Pabpn1l -/- MII oocytes. Of the 2401 transcripts upregulated in Pabpn1l-/- MII oocytes, 1523 transcripts (63.4%) were also upregulated in Btg4 -/- MII oocytes, while only 53 transcripts (2.2%) were upregulated in Ythdf2 -/- MII oocytes. We documented that transcripts in zygotes derived from Pabpn1l -/- oocytes have a longer poly(A) tail than the control group, a phenomenon similar to that in Btg4-/- mice. Surprisingly, the poly(A) tail of these mRNAs was significantly shorter in the Pabpn1l -/- MII oocytes than in the Pabpn1l +/+. These results suggest that PABPN1L is involved in BTG4-mediated maternal mRNA degradation, and may antagonize poly(A) tail shortening in oocytes independently of its involvement in maternal mRNA degradation. Thus, PABPN1L variants could be a genetic marker of female infertility.

scholarly journals Eosinophil-derived IL-13 promotes emphysema

2019 ◽  
Vol 53 (5) ◽  
pp. 1801291 ◽  
Author(s):  
Alfred D. Doyle ◽  
Manali Mukherjee ◽  
William E. LeSuer ◽  
Tyler B. Bittner ◽  
Saif M. Pasha ◽  
...  
Keyword(s):  
Mouse Model ◽  
Inflammatory Responses ◽  
Pulmonary Inflammation ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Chronic Type ◽  
Obstructive Pulmonary Disease ◽  
Lung Eosinophilia

The inflammatory responses in chronic airway diseases leading to emphysema are not fully defined. We hypothesised that lung eosinophilia contributes to airspace enlargement in a mouse model and to emphysema in patients with chronic obstructive pulmonary disease (COPD).A transgenic mouse model of chronic type 2 pulmonary inflammation (I5/hE2) was used to examine eosinophil-dependent mechanisms leading to airspace enlargement. Human sputum samples were collected for translational studies examining eosinophilia and matrix metalloprotease (MMP)-12 levels in patients with chronic airways disease.Airspace enlargement was identified in I5/hE2 mice and was dependent on eosinophils. Examination of I5/hE2 bronchoalveolar lavage identified elevated MMP-12, a mediator of emphysema. We showed, in vitro, that eosinophil-derived interleukin (IL)-13 promoted alveolar macrophage MMP-12 production. Airspace enlargement in I5/hE2 mice was dependent on MMP-12 and eosinophil-derived IL-4/13. Consistent with this, MMP-12 was elevated in patients with sputum eosinophilia and computed tomography evidence of emphysema, and also negatively correlated with forced expiratory volume in 1 s.A mouse model of chronic type 2 pulmonary inflammation exhibited airspace enlargement dependent on MMP-12 and eosinophil-derived IL-4/13. In chronic airways disease patients, lung eosinophilia was associated with elevated MMP-12 levels, which was a predictor of emphysema. These findings suggest an underappreciated mechanism by which eosinophils contribute to the pathologies associated with asthma and COPD.

Visualization of pulmonary inflammation using noninvasive fluorescence molecular imaging

2008 ◽  
Vol 104 (3) ◽  
pp. 795-802 ◽  
Author(s):  
Jodi Haller ◽  
Damon Hyde ◽  
Nikolaos Deliolanis ◽  
Ruben de Kleine ◽  
Mark Niedre ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Quantitative Imaging ◽  
Pulmonary Inflammation ◽  
Small Animal ◽  
Mouse Lung ◽  
Chronic Obstructive ◽  
Therapy Assessment ◽  
Fluorescence Molecular Imaging

The ability to visualize molecular processes and cellular regulators of complex pulmonary diseases such as asthma, chronic obstructive pulmonary disease (COPD), or adult respiratory distress syndrome (ARDS), would aid in the diagnosis, differentiation, therapy assessment and in small animal-based drug-discovery processes. Herein we report the application of normalized transillumination and fluorescence molecular tomography (FMT) for the noninvasive quantitative imaging of the mouse lung in vivo. We demonstrate the ability to visualize and quantitate pulmonary response in a murine model of LPS-induced airway inflammation. Twenty-four hours prior to imaging, BALB/c female mice were injected via tail vein with 2 nmol of a cathepsin-sensitive activatable fluorescent probe (excitation: 750 nm; emission: 780 nm) and 2 nmol of accompanying intravascular agent (excitation: 674 nm; emission: 694 nm). Six hours later, the mice were anesthetized with isoflurane and administered intranasal LPS in sterile 0.9% saline in 25 μl aliquots (one per nostril). Fluorescence molecular imaging revealed the in vivo profile of cysteine protease activation and vascular distribution within the lung typifying the inflammatory response to LPS insult. Results were correlated with standard in vitro laboratory tests (Western blot, bronchoalveolar lavage or BAL analysis, immunohistochemistry) and revealed good correlation with the underlying activity. We demonstrated the capacity of fluorescence tomography to noninvasively and longitudinally characterize physiological, cellular, and subcellular processes associated with inflammatory disease burden in the lung. The data presented herein serve to further evince fluorescence molecular imaging as a technology highly appropriate for the biomedical laboratory.

scholarly journals Genome-wide methylation and expression analyses reveal the epigenetic landscape of immune-related diseases for tobacco smoking

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Ying Mao ◽  
Peng Huang ◽  
Yan Wang ◽  
Maiqiu Wang ◽  
Ming D. Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cigarette Smoke ◽  
Tobacco Smoking ◽  
Molecular Mechanisms ◽  
Functional Enrichment ◽  
Chronic Obstructive ◽  
Rna Seq ◽  
Immune System Diseases ◽  
Genome Wide ◽  
A Genome

Abstract Background Smoking is a major causal risk factor for lung cancer, chronic obstructive pulmonary disease (COPD), cardiovascular disease (CVD), and is the main preventable cause of deaths in the world. The components of cigarette smoke are involved in immune and inflammatory processes, which may increase the prevalence of cigarette smoke-related diseases. However, the underlying molecular mechanisms linking smoking and diseases have not been well explored. This study was aimed to depict a global map of DNA methylation and gene expression changes induced by tobacco smoking and to explore the molecular mechanisms between smoking and human diseases through whole-genome bisulfite sequencing (WGBS) and RNA-sequencing (RNA-seq). Results We performed WGBS on 72 samples (36 smokers and 36 nonsmokers) and RNA-seq on 75 samples (38 smokers and 37 nonsmokers), and cytokine immunoassay on plasma from 22 males (9 smokers and 13 nonsmokers) who were recruited from the city of Jincheng in China. By comparing the data of the two groups, we discovered a genome-wide methylation landscape of differentially methylated regions (DMRs) associated with smoking. Functional enrichment analyses revealed that both smoking-related hyper-DMR genes (DMGs) and hypo-DMGs were related to synapse-related pathways, whereas the hypo-DMGs were specifically related to cancer and addiction. The differentially expressed genes (DEGs) revealed by RNA-seq analysis were significantly enriched in the “immunosuppression” pathway. Correlation analysis of DMRs with their corresponding gene expression showed that genes affected by tobacco smoking were mostly related to immune system diseases. Finally, by comparing cytokine concentrations between smokers and nonsmokers, we found that vascular endothelial growth factor (VEGF) was significantly upregulated in smokers. Conclusions In sum, we found that smoking-induced DMRs have different distribution patterns in hypermethylated and hypomethylated areas between smokers and nonsmokers. We further identified and verified smoking-related DMGs and DEGs through multi-omics integration analysis of DNA methylome and transcriptome data. These findings provide us a comprehensive genomic map of the molecular changes induced by smoking which would enhance our understanding of the harms of smoking and its relationship with diseases.

scholarly journals Xiangshao Granule Exerts Antidepressive Effects in a Depression Mouse Model by Ameliorating Deficits in Hippocampal BDNF and TrkB

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Yi Chen ◽  
Jie Liu ◽  
Xiaoting Wu ◽  
Edouard Collins Nice
Keyword(s):  
Treatment Group ◽  
Mouse Model ◽  
Molecular Mechanisms ◽  
Open Field Test ◽  
The Body ◽  
Control Group ◽  
Therapeutic Effects ◽  
Model Group ◽  
Depression Group ◽  
Antidepressive Effects

This study explores the therapeutic effects of Xiangshao granules in a mouse depression model and examines the potential molecular mechanisms involved. After 21 consecutive days of chronic stress challenge, all mice were divided into three groups: control group, depression group, and Xiangshao granule treatment group. On the 22nd day, rats in the Xiangshao granule treatment group received Xiangshao granules via gastrogavage for 3 consecutive weeks. Depression group mice showed a significant reduction of crossings (P<0.01) but not rearings (P<0.05). Serum CRH, CORT, and ACTH levels were significantly increased in depression mice compared with control (P<0.05) and the expression levels of hippocampal BDNF and TrkB were reduced in the model group (P<0.05). However, Xiangshao granule treatment remarkably rescued the decrease in the body weight (P<0.05), increased crossings in the open field test (P<0.05), upregulated the expression of hippocampal BDNF and TrkB expression, and reduced the serum CRH, CORT, and ACTH concentrations compared with the depression group (P<0.05). Collectively, these results demonstrated that Xiangshao granule could effectively induce antidepressive effects in the depression mouse model by ameliorating the expression of hippocampal BDNF and TrkB.

Identification of immune-related genes in thymus of breast cancer mouse model exposed to different calorie restriction

2019 ◽  
Vol 44 (5) ◽  
pp. 635-645
Author(s):  
Zehra Omeroglu Ulu ◽  
Salih Ulu ◽  
Soner Dogan ◽  
Bilge Guvenc Tuna ◽  
Nehir Ozdemir Ozgenturk
Keyword(s):  
Breast Cancer ◽  
Mouse Model ◽  
Calorie Restriction ◽  
Molecular Mechanisms ◽  
Transcriptional Profiling ◽  
Rna Seq ◽  
Expression Levels ◽  
Thymus Tissue ◽  
Different Types ◽  
Immune Related Genes

Abstract Introduction In the present study, RNA sequencing-mediated transcriptome analysis was performed in order to elucidate the molecular mechanisms of the immune response for different types of calorie restriction (CR) application using MMTV-TGF-α breast cancer mouse model. Methods Animals were applied to three different dietary regiments; ad libitum (AL), chronic calorie restriction (CCR) and intermittent calorie restriction (ICR). Using thymus tissues, 6091 differentially expressed genes (DEGs) were identified in three dietary groups. After clustering of total of 6091 DEGs using Gene Ontology (GO) categories, a total of 400 genes were identified to be involved in immune system process (GO:0002376) GO categories. KEGG pathway and gene co-expression network analysis of these immune-related DEGs were done using String database. The results were confirmed with measuring mRNA expression levels of four selected immune-related DEGs genes (Casp3, Thy1, IL-16 and CD4) using quantitative real-time PCR (qPCR). Results The expression levels of immune-related genes were different in three RNA-seq data. Conclusion The results provide useful information to investigate the immune-related transcriptional profiling in thymus tissue of breast cancer mouse model applied to two different types of CR and to identify the specific functional immune related genes in response to CR during cancer development.

scholarly journals Integrated Analysis of Multiple Microarray Studies to Identify Novel Gene Signatures in Ulcerative Colitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Zi-An Chen ◽  
Yu-Feng Sun ◽  
Quan-Xu Wang ◽  
Hui-Hui Ma ◽  
Zhi-Zhao Ma ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Mouse Model ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Rank Aggregation ◽  
Integrated Analysis ◽  
Control Group ◽  
Functional Modules ◽  
Ppi Network ◽  
Hub Genes

Background: Ulcerative colitis (UC) is a chronic, complicated, inflammatory disease with an increasing incidence and prevalence worldwide. However, the intrinsic molecular mechanisms underlying the pathogenesis of UC have not yet been fully elucidated.Methods: All UC datasets published in the GEO database were analyzed and summarized. Subsequently, the robust rank aggregation (RRA) method was used to identify differentially expressed genes (DEGs) between UC patients and controls. Gene functional annotation and PPI network analysis were performed to illustrate the potential functions of the DEGs. Some important functional modules from the protein-protein interaction (PPI) network were identified by molecular complex detection (MCODE), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG), and analyses were performed. The results of CytoHubba, a plug for integrated algorithm for biomolecular interaction networks combined with RRA analysis, were used to identify the hub genes. Finally, a mouse model of UC was established by dextran sulfate sodium salt (DSS) solution to verify the expression of hub genes.Results: A total of 6 datasets met the inclusion criteria (GSE38713, GSE59071, GSE73661, GSE75214, GSE87466, GSE92415). The RRA integrated analysis revealed 208 significant DEGs (132 upregulated genes and 76 downregulated genes). After constructing the PPI network by MCODE plug, modules with the top three scores were listed. The CytoHubba app and RRA identified six hub genes: LCN2, CXCL1, MMP3, IDO1, MMP1, and S100A8. We found through enrichment analysis that these functional modules and hub genes were mainly related to cytokine secretion, immune response, and cancer progression. With the mouse model, we found that the expression of all six hub genes in the UC group was higher than that in the control group (P &lt; 0.05).Conclusion: The hub genes analyzed by the RRA method are highly reliable. These findings improve the understanding of the molecular mechanisms in UC pathogenesis.

scholarly journals Therapeutic Effect Observation of Tiotropium Bromide in the Treatment of Overlap Syndrome

2020 ◽  
Vol 3 (1) ◽  
pp. 15
Author(s):  
Yunchao Huang ◽  
Ting Wang
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Sleep Apnea ◽  
Pulmonary Function ◽  
Pulmonary Disease ◽  
Overlap Syndrome ◽  
Tiotropium Bromide ◽  
Control Group ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Obstructive Sleep

Objective: To study the M receptor blocker on inhalation in patients with overlap syndrome (chronic obstructive pulmonary disease and Obstructive sleep apnea syndrome) curative effect analysis. Methods: 25 patients with overlap syndrome as the experimental group, chronic obstructive pulmonary disease patients (30) as control group, patients with overlap syndrome use inhaled tiotropium powder treat 30 days, to observe the changes of pulmonary function, polysomnography, and other indicators after treatment. Results: Overlap syndrome were treated by tiotropium bromide inhalation powder, has improved the pulmonary function, the sleep apnea index and lowest nocturnal oxygen saturation after treatment. Conclusion: tiotropium bromide has a preferable effective in treatment of overlap syndrome, COPD and OSAHS are interacting with each other.

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