Gene expression in TNF treated rat aortic rings cultured in collagen or fibrin gels.
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE23153 | GEO | 2011/07/21
SECONDARY ACCESSION(S): PRJNA131573
REPOSITORIES: GEO
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Project description:Angiogenesis in cultures of rat aorta begins with neovessels sprouting from the aortic explant within the first three days of culture. We used microarrys to examine the effects of TNF-alpha on gene expression in both fibrin and collagen gels during the first 48 hours or culture. Rat aortic rings were cultured in either collagen or fibrin maticies. Half of the cultures from each matrix group were treated with 10ng/ml recombinant rat TNF-alpha, and half were left untreated. These cultures were used to prepare total RNA
2011-07-20 | E-GEOD-23153 | biostudies-arrayexpress
Project description:Angiogenesis in collagen gel cultures of rat aorta begins with neovessels sprouting from the aortic explant within the first three days of culture. We used microarrays to detail the pattern of gene expression underlying initial 24 hours of growth, prior to the sprouting of visible neovessles, and identified distinct classes of up-regulated genes during this process.
2011-07-21 | GSE23152 | GEO
Project description:Angiogenesis in collagen gel cultures of rat aorta begins with neovessels sprouting from the aortic explant within the first three days of culture. We used microarrays to detail the pattern of gene expression underlying initial 24 hours of growth, prior to the sprouting of visible neovessles, and identified distinct classes of up-regulated genes during this process. Either freshly harvested aortic rings, representing day 0, or collagen gel cultures of rat aorta were grown in serum free medium and used to prepare total RNA.
2011-07-20 | E-GEOD-23152 | biostudies-arrayexpress
Project description:Collagen- and fibrin-based gels are extensively used to study cell behaviour. However, 2D-3D, collagen-fibrin, and in vivo-in vitro comparisons of gene expression, cell shape and mechanotransduction have not been reported. Here we compared chick tendon fibroblasts (CTFs) at three stages of embryonic development with CTFs cultured in collagen- or fibrin-based tissue engineered constructs (TECs).
2015-09-30 | E-MTAB-3488 | biostudies-arrayexpress
Project description:We hypothesized that generating spinal motor neurons (sMNs) from human induced pluripotent stem cell (hiPSC)-derived neural aggregates (NAs) using a chemically-defined differentiation protocol would be more effective inside of 3D fibrin hydrogels compared to 2D poly-L-ornithine(PLO)/laminin-coated tissue culture plastic surfaces. We performed targeted RNA-Seq using next generation sequencing to determine the substrate-specific differences in gene expression that regulate cell phenotype. Cells cultured on both substrates expressed sMN genes CHAT and MNX1, though persistent WNT signaling contributed to a higher expression of genes associated with interneurons in NAs cultured in 3D fibrin scaffolds. Cells in fibrin also expressed lower levels of astrocyte progenitor genes and higher levels of the neuronal-specific gene TUBB3, suggesting a purer population of neurons compared to 2D cultures. STATEMENT OF SIGNIFICANCE: Fibrin scaffolds can support the neuronal differentiation of pluripotent stem cells. This study provides insight into how fibrin hydrogels affect neuronal induction by analyzing of the signaling pathways activated during the differentiation process. These insights can then be used to tailor the properties of these hydrogels to optimize the generation of sMNs for regenerative medicine applications.
2017-01-17 | GSE79442 | GEO
Project description:Life-threatening thrombotic events and neurological symptoms are prevalent in COVID-19 and are persistent in patients with long COVID experiencing post-acute sequelae of SARS-CoV-2 infection1,2,3,4. Despite the clinical evidence1,5,6,7, the underlying mechanisms of coagulopathy in COVID-19 and its consequences in inflammation and neuropathology remain poorly understood and treatment options are insufficient. Fibrinogen, the central structural component of blood clots, is abundantly deposited in the lungs and brains of patients with COVID-19, correlates with disease severity and is a predictive biomarker for post-COVID-19 cognitive deficits1,5,8,9,10. Here we show that fibrin binds to the SARS-CoV-2 spike protein, forming proinflammatory blood clots that drive systemic thromboinflammation and neuropathology in COVID-19. Fibrin, acting through its inflammatory domain, is required for oxidative stress and macrophage activation in the lungs, whereas it suppresses natural killer cells, after SARS-CoV-2 infection. Fibrin promotes neuroinflammation and neuronal loss after infection, as well as innate immune activation in the brain and lungs independently of active infection. A monoclonal antibody targeting the inflammatory fibrin domain provides protection from microglial activation and neuronal injury, as well as from thromboinflammation in the lung after infection. Thus, fibrin drives inflammation and neuropathology in SARS-CoV-2 infection, and fibrin-targeting immunotherapy may represent a therapeutic intervention for patients with acute COVID-19 and long COVID.
2024-06-28 | GSE268812 | GEO
Project description:Life-threatening thrombotic events and neurological symptoms are prevalent in COVID-19 and are persistent in patients with long COVID experiencing post-acute sequelae of SARS-CoV-2 infection1,2,3,4. Despite the clinical evidence1,5,6,7, the underlying mechanisms of coagulopathy in COVID-19 and its consequences in inflammation and neuropathology remain poorly understood and treatment options are insufficient. Fibrinogen, the central structural component of blood clots, is abundantly deposited in the lungs and brains of patients with COVID-19, correlates with disease severity and is a predictive biomarker for post-COVID-19 cognitive deficits1,5,8,9,10. Here we show that fibrin binds to the SARS-CoV-2 spike protein, forming proinflammatory blood clots that drive systemic thromboinflammation and neuropathology in COVID-19. Fibrin, acting through its inflammatory domain, is required for oxidative stress and macrophage activation in the lungs, whereas it suppresses natural killer cells, after SARS-CoV-2 infection. Fibrin promotes neuroinflammation and neuronal loss after infection, as well as innate immune activation in the brain and lungs independently of active infection. A monoclonal antibody targeting the inflammatory fibrin domain provides protection from microglial activation and neuronal injury, as well as from thromboinflammation in the lung after infection. Thus, fibrin drives inflammation and neuropathology in SARS-CoV-2 infection, and fibrin-targeting immunotherapy may represent a therapeutic intervention for patients with acute COVID-19 and long COVID.
2024-06-28 | GSE268810 | GEO
Project description:Activation of innate immunity and deposition of blood-derived fibrin in the central nervous system (CNS) occur in autoimmune and neurodegenerative diseases, including multiple sclerosis (MS) and Alzheimer’s disease (AD). However, mechanisms linking blood-brain barrier (BBB) disruption with neurodegeneration are poorly understood, and exploration of fibrin as a therapeutic target has been limited by its beneficial clotting functions. Here we report the generation of monoclonal antibody 5B8 targeted against the cryptic fibrin epitope γ377-395 to selectively inhibit fibrin-induced inflammation. 5B8 suppressed fibrin-induced proinflammatory gene expression, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, and oxidative stress. In animal models of MS and AD, 5B8 entered the CNS and bound to parenchymal fibrin, and its therapeutic administration reduced innate immune activation and neurodegeneration without interfering with clotting. Thus, fibrin-targeting immunotherapy inhibits autoimmune- and amyloid-driven neurotoxicity and may have clinical benefit without globally suppressing innate immunity or interfering with coagulation in diverse neurological diseases.
2019-02-13 | GSE118921 | GEO
Project description:The extracellular matrix (ECM)-regulated phenotypic plasticity is crucial for metastatic progression of triple negative breast cancer (TNBC). To investigate the effect of matrix cues on phenotypic plasticity, we embedded triple negative DU4475 cells from suspension culture into mechanically tunable fibrin gels or basement membrane extract (Matrigel). Cells in suspension culture and matrix cultures showed divergent gene expression profiles, with specific gene expression signatures depending on the biochemical composition and stiffness of the matrix.
2023-04-05 | GSE228939 | GEO
Project description:Purpose:To identify transcriptional changes in human endothelial cells (HUVEC) both during normal sprouting angiogenesis (different time points) and with Slug overexpression (different Slug expression), in a 3D fibrin-gel bead angiogenesis Methods: Angiogenic endothelial cell with different level of Slug expression (normal and overexpressing) at different stage (early/sprouting and late/lumen formation) were harvested from a 3D fibrin-gel bead angiogenesis assay. Their transcriptom profile was generated by Next Generation RNA-sequencing as single reads, performed on an Illumina HiSeq 2500 platform, using three donor HUVEC lines.At least 30 million reads per sample were sequenced. Quality control was performed on data using FASTQC(v. 0.11.2), and reads were trimmed using Trimmomatic(v.0.32) with Illumina TruSeq adapter sequences using a PHRED quality score 15 and minimum length 20 bases. Trimmed reads were then aligned to the human hg19 reference genome using the Ensembl GRCh37 annotations and post processed using Tophat2(v.2.0.12), Bowtie2(v.2.2.3) and Samtools(v.0.1.19). Expression levels were quantified both with FPKM (Fragment per kilobase per million mapped reads) using Cufflinks(v. 2.1.1) and with raw counts using HTSeq(v.0.6.1p1.). Differential analysis was done using DESeq2 and significant genes were considered (p-value < 0.05, 2 fold change). K-means clustering was performed to extract dynamic gene clusters based on differential expression between GFP and SLUG knockdown time-points. Gene set enrichment analysis (GSEA) was performed on expressed genes to identify significant gene sets across sample comparisons. Additional gene ontology analysis was performed for each cluster and reported using Metascape. Clustering was performed in R and heatmaps were generated using JavaTree. Results: Using several different gene expression analysis platforms, we found consistent and significant changes, during both normal angiogenesis and with Slug overexpression, in genes related to proliferation, migraion, cell morphology/polarity and junction regulations, all of which are consistent with a partial-EMT program. We also found changes in Notch signaling components in Slug overexpressing cells. Changes in specific genes related to EMT and Notch signaling were validated with both qPCR and WB. Conclusion: This is the first comprehensive transcriptome analysis in human angiogenic EC during normal and excessive sprouting induced by Slug expression in an in vitro 3D angiogenesis assay system. We conclude that a partial-EndoMT is necessary for normal angiogenesis and that endothelial Slug expresion level regulates Notch signaling to determines at least partly the extent of EC's commitment towards a mesenchymal identity.
2020-08-01 | GSE154546 | GEO