Transcriptomic analysis by RNA-seq unveils distinct gene expression profile of U397 cells depleted of NSPs
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE142662 | GEO | 2021/04/02
REPOSITORIES: GEO
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Project description:ATAC-Seq was used to investigate the impact of genetic ablation of neutrophil serine proteases CTSG, ELANE, and PRTN3 on chromatin dynamics and accessibility. Differential analysis identified thousands of peaks with elevated accessibility in independent ΔNSP clones relative to controls.
2021-04-02 | GSE142660 | GEO
Project description:Abstract<br>BACKGROUND: Gene expression profiling (GEP) in cells obtained from peripheral blood has demonstrated to be a very useful approach for biomarker discovery and for studying molecular pathogenesis of prevalent diseases. While there is limited literature availble on gene expression markers associated to Chronic Obstructive Pulmonary Disease (COPD), the transcriptomic picture associated to critical respiratory illness in this disease is not known to the present moment. <br>RESULTS: By using Agilent microarray chips, we have profiled gene expression signatures in whole blood of 28 COPD patients hospitalized with distinct degree of respiratory compromise.12 of them needed of admission to the ICU, while 16 were admitted to the Respiratory Medicine Service. GeneSpring GX 11.0 software was used for performing statistical comparison of transcript levels between ICU and non ICU patients. Ingenuity pathway analysis 8.5 (IPA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to select, annotate and visualize genes by function and pathway (gene ontology). T-test evidenced 1501 genes differentially expressed between ICU and non ICU patients. IPA and KEGG analysis of the most representative biological functions revealed that ICU patients showed increased levels of neutrohil gene transcripts, being [cathepsin G (CTSG)], [elastase, neutrophil expressed (ELANE)], [proteinase 3 (PRTN3)], [myeloperoxidase (MPO)], [cathepsin D (CTSD)], [defensin, alpha 3, neutrophil-specific (DEFA3)], azurocidin 1 (AZU1)], [bactericidal/permeability-increasing protein (BPI)] the most representative ones. Proteins codified by these genes form part of the azurophilic granules of neutrophils and are involved in both antimicrobial defence and tissue damage. This ?neutrophil signature? was paralleled by necessity of advanced respiratory and vital support, and presence of bacterial infection.<br>CONCLUSION: study of transcriptomic signatures in blood suggests a central role of neutrophil proteases in COPD patients with critical respiratory illness. Measurement / modulation of the expression of these genes could represent an option for clinical monitoring and treatment of severe COPD exacerbations. <br><br>Keywords: COPD, critical, expression, gene, microarray, neutrophil, proteases.<br><br>
2013-03-12 | E-MEXP-3589 | biostudies-arrayexpress
Project description:Andrographolide sulfonate (Andro-S), a sulfonation derivative of andrographolide, is known to be effective in treating inflammation-related diseases, while the underlying mechanisms and global protein alterations in response to Andro-S remain unknown. This study aimed to investigate the pharmacological effects and potential targets of Andro-S in a murine model of acute lung injury (ALI). ALI was induced by aerosolized lipopolysaccharide (LPS) exposure before treatment with Andro-S. Inflammatory state of each treatment group was determined by histological analysis and quantification of inflammatory markers. Differentially expressed proteins in lung tissues were identified by an iTRAQ-based quantitative proteomic approach and further confirmed by immunohistochemistry analysis. Administration of Andro-S alleviated LPS-induced histological changes in the lung and reduced the expression of inflammatory markers in serum, bronchoalveolar fluid and lung tissues. Proteomic analysis identified 34 differentially expressed proteins from a total of 2,234 quantified proteins in the lung. According to bioinformatics analysis, neutrophil elastase (ELANE), Cathepsin G (CTSG) and myeloperoxidase (MPO), three neutrophil-derived proteases related to immune system process and defense responses to fungi were chosen as potential targets of Andro-S. Further immunohistochemistry analysis confirmed the inhibitory effects of Andro-S on LPS-induced ELANE, CTSG and MPO up-regulation. These results indicate that Andro-S suppressed the severity of LPS-induced ALI, possibly by attenuating the expression of and neutrophil-derived proteases.
2018-10-22 | PXD008552 | Pride
Project description:Purpose: The goals of this study are to compare NGS-derived liver transcriptome profiling (RNA-seq). Methods: Alb-CRE/rosa26 rtTA/SREBP(S1a/Ctrl) vs Alb-CRE/rosa26 rtTA/SREBP/TRE-ETP (S1a/ETP) transgenic mice liver (RNAseq) Results: an increase in the levels of markers that are important for immune responses and inflammation and initiating and promoting tumour growth . In addition, genes abundantly expressed in neutrophils (Elane, Mpo, Ngp, Prtn3, Chil3, Cd177, S100a8, S100a9, and Lcn-2) were up-regulated Conclusions: Our data reveal that ETP can act as a “second hit” during NAFLD progression and can play an important role in the development of NASH and hepatocellular carcinoma (HCC).
2020-11-05 | GSE144653 | GEO
Project description:The purpose of this study is to learn the dynamic transcriptomic and molecular changes during neutrophil development. We investigated the gene expression profiles of purified morphology-defined neutrophil populations. Promyelocytes (PMs), myelocytes (MCs), metamyelocytes (MMs), band neutrophils and segmented neutrophils (BN/SNs) were isolated by FACS based on differential expression of C-Kit and Ly6g.Their identities were confirmed by morphological examination. Bulk RNA sequencing was then performed to reveal the gene expression profiles and molecular signatures of each cell population. Detailed analysis of gene expression revealed that MBs highly expressed the stem cell marker Cd34 and translation-related genes such as Eef1a1, while the highest expression of primary granule-related genes such as Mpo, Elane, Prtn3, and Cstg was detected in the PM population. MCs and MMs were highly proliferative neutrophils expressing high levels of cell cycle-related genes which were significantly downregulated in mature neutrophils. Finally, this study provides a framework for the detail study of the neutrophil development and for the future application in the modulation of the granulopoiesis under pathological conditions.
2020-05-27 | GSE137538 | GEO
Project description:Cordyceps militaris and Cordyceps sinensis belong to belong to the same genus, but the different species, with immunity improvement, antibacterial, and antihypertensive effect, and the studies on the functions of Cordyceps militaris mainly focus on those of its polysaccharides and polypeptides. The latest studies have found that some of the polypeptides with immunomodulatory effect can widely regulate immune functions at multiple levels, improve immunity, and enhance immune functions to ensure the healthy body, showing an important significance. Cordyceps militaris polypeptide prepared with the enzymolysis method was taken as the research object in this study. The differentially expressed genes and the related cell signal transduction pathway were screened by mRNA expression microarray. STEM 1.3.6 software was used for the clustering of the gene functions, and David and KEGG database were applied for the analysis of the related functions. 1748 differentially expressed genes were selected finally and three of them were validated by qPCR. The results showed that gene Hist1h2bp, Ctsg, and Elane were involved in the regulation of Cordyceps militaris on the immune activity of mice. Gene Hist1h2bp, Ctsg and Elan may be the potential targets of Cordyceps militaris polypeptide, which may provide an important theory basis for the further research and development of Cordyceps militaris polypeptide.
2019-05-01 | GSE81389 | GEO
Project description:Background/aims: Changes in gene expression profiles among individuals with inflammatory bowel diseases (IBDs) could potentially influence the responsiveness to anti-TNF treatment. The aim of this study was to identify genes that could serve as predictors of early response to anti-TNF therapies in pediatric IBD patients prior to the initiation of treatment.Methods: We conducted a prospective, longitudinal, and multicenter study, enrolling 24 pediatric IBD patients aged less than 18 years who were initiating treatment with either infliximab or adalimumab. RNA-seq from blood samples was analyzed using the DESeq2 library by comparing responders and non-responders to anti-TNF drugs. Results: Bioinformatic analyses unveiled 102 differentially expressed genes, with 99 genes exhibiting higher expression in responders compared to non-responders prior to the initiation of anti-TNF therapy. Functional enrichment analyses highlighted defense response to Gram-negative bacteria (FDR =2.3 ×10–7) as the most significant biological processes, and hemoglobin binding (FDR =0.002), as the most significant molecular function. Gene Set Enrichment Analysis (GSEA) revealed notable enrichment in transcriptional misregulation in cancer (FDR =0.016). Notably, 13 genes (CEACAM8, CEACAM6, CILP2, COL17A1, OLFM4, INHBA, LCN2, LTF, MMP8, DEFA4, PRTN3, AZU1, and ELANE) were selected for validation, and a consistent trend of increased expression in responders prior to drug administration was observed for most of these genes, with findings for 4 of them being statistically significant (CEACAM8, LCN2, LTF2, and PRTN3). Conclusions: We identified 102 differentially expressed genes involved in the response to anti-TNF drugs in children with IBDs and validated CEACAM8, LCN2, LTF2, and PRTN3. Genes participating in defense response to Gram-negative bacterium, serine-type endopeptidase activity, and transcriptional misregulation in cancer are good candidates for anticipating the response to anti-TNF drugs in children with IBDs.
2024-02-26 | GSE247146 | GEO
Project description:Chronic obstructive pulmonary disease (COPD) is India's second largest cause of death and is largely caused by smoking. Asymptomatic smokers develop COPD due to genetic, environmental, and molecular variables, making early screening crucial. Data-independent acquisition mass spectrometry (DIA-MS) proteomics offers an unbiased method to analyze proteomic profiles. This study is the first to use DIA-based proteomics to analyze individual serum samples from three distinct male cohorts: healthy individuals (n=10), asymptomatic smokers (n=10), and COPD patients (n=10). This comprehensive approach identified 667 proteins with a 1% false discovery rate. Differentially expressed proteins included 40 in the normal versus asymptomatic comparison, 88 in the COPD versus normal comparison, and 40 in the COPD versus asymptomatic comparison. Among them, PRDX6, ELANE, PRKCSH, PRTN3, and MNDA could help differentiate COPD from asymptomatic smokers, while ELANE, H3-3A, IGHE, SLC4A1, and SERPINA11 could differentiate COPD from healthy subjects. Pathway enrichment and protein-protein interaction analyses revealed significant alterations in hemostasis, immune system functions, fibrin clot formation, and post-translational protein modifications. Key proteins were validated using a parallel reaction monitoring assay. DIA data are available via ProteomeXchange with identifier PXD055242. Our findings reveal key protein classifiers in COPD patients, asymptomatic smokers, and healthy individuals, helping clinicians understand disease pathobiology and improve disease management and quality of life.
2024-11-13 | PXD055242 | Pride
Project description:In CUMS mice, neutrophils can infiltrate brain parenchyma and induce neuroinflammatory responses. To identify potential mediators, we analyzed the gene expression profiles of bone marrow neutrophils from mice subjected to CUMS and compared them with those of control mice. Interestingly, among the genes notably associated with neutrophil functions were Elane and Mpo, the crucial granule proteins of neutrophils that mediate chronic inflammation. Our study demonstrated that neutrophil-specific Elane knockout reduced neutrophil infiltration into the brain parenchyma and alleviated neuroinflammation. Elane plays a critical role in modulating the influence of peripheral neutrophils on brain.
2024-12-17 | GSE271724 | GEO
Project description:The intratumoral activity of chemokine system has important roles in cancer immunotherapy strategies.One of the mechanisms of immune checkpoint blocking (ICB)resistance may be the dysfunction of chemokine signaling. Here, we first report that KRAS mutation in LUAD cells up-regulates the expression of protease 3 (PRTN3), that inhibits cytotoxic immune cell activation in the tumor microenvironment by inhibiting the CXCL9/CXCR3 axis, providing an unconventional mechanism for tumor immune escape. Further mechanism studies demonstrated that PRTN3 was up-regulated by c-Myc transcription and secreted into the tumor microenvironment, where CXCL9 was inactivated by proteolysis, and finally result in inhibiting the activation of natural killer (NK) and CD8+ T cells. Meanwhile, samples from LUAD patients with high PRTN3 expression showed low CXCL9 activity. Furthermore, application of a hydrolysis-resistant CXCL9 protein (H-R CXCL9) effectively improves the immunomodulate effect in LUAD patient organoids. Importantly, PRTN3 knockdown increased the susceptibility of KRAS mutant cells to Anti-pd-1 therapy. Thus, we have identified a previously unknown tumor immune-suppressive mechanism and provided an immunotherapeutic target to improve the effectiveness of ICB therapy in KRAS mutant LUAD.
2024-07-13 | GSE271713 | GEO