Cortistatin deficiency reveals a dysfunctional brain endothelium with impaired gene pathways, exacerbated immune activation, and disrupted barrier integrity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA855254 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19963017_1.fastq.gz | Fastqsanger.gz | |||
| SRR19963017_2.fastq.gz | Fastqsanger.gz | |||
| SRR19963018_1.fastq.gz | Fastqsanger.gz | |||
| SRR19963018_2.fastq.gz | Fastqsanger.gz | |||
| SRR19963019_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:Background: Brain activity governing cognition and behaviour depends on the fine-tuned microenvironment provided by a tightly controlled blood-brain barrier (BBB). Brain endothelium dysfunction is a hallmark of BBB breakdown in most neurodegenerative/neuroinflammatory disorders. Therefore, the identification of new endogenous molecules involved in endothelial cell disruption is essential to better understand BBB dynamics. Cortistatin is a neuroimmune mediator with anti-inflammatory and neuroprotective properties that exerts beneficial effects on the peripheral endothelium. However, its role in the healthy and injured brain endothelium remains to be evaluated. Herein, this study aimed to investigate the potential function of endogenous and therapeutic cortistatin in regulating brain endothelium dysfunction in a neuroinflammatory/neurodegenerative environment. Methods: Wild-type and cortistatin-deficient murine brain endothelium and human cells were used for an in vitro barrier model, where a simulated ischemia-like environment was mimicked. Endothelial permeability, junction integrity, and immune response in the presence and absence of cortistatin were evaluated using different size tracers, immunofluorescence labelling, qPCR, and ELISA. Cortistatin molecular mechanisms underlying brain endothelium dynamics were assessed by RNA-sequencing analysis. Cortistatin role in BBB leakage was evaluated in adult mice injected with LPS. Results: The endogenous lack of cortistatin predisposes endothelium weakening with increased permeability, tight-junctions breakdown, and dysregulated immune activity. We demonstrated that both damaged and uninjured brain endothelial cells isolated from cortistatin-deficient mice, present a dysregulated and/or deactivated genetic programming. These pathways, related to basic physiology but also crucial for the repair after damage (e.g., extracellular matrix remodelling, angiogenesis, response to oxygen, signalling, and metabolites transport), are dysfunctional and make brain endothelial barrier lacking cortistatin non-responsive to any further injury. Treatment with cortistatin reversed in vitro hyperpermeability, tight-junctions disruption, inflammatory response, and reduced in vivo BBB leakage. Conclusions: The neuropeptide cortistatin has a key role in the physiology of the cerebral microvasculature and its presence is crucial to develop a canonical balanced response to damage. The reparative effects of cortistatin in the brain endothelium were accompanied by the modulation of the immune function and the rescue of barrier integrity. Cortistatin-based therapies could emerge as a novel pleiotropic strategy to ameliorate neuroinflammatory/neurodegenerative disorders with disrupted BBB.
2023-09-01 | GSE207405 | GEO
Project description:BackgroundBrain activity governing cognition and behaviour depends on the fine-tuned microenvironment provided by a tightly controlled blood-brain barrier (BBB). Brain endothelium dysfunction is a hallmark of BBB breakdown in most neurodegenerative/neuroinflammatory disorders. Therefore, the identification of new endogenous molecules involved in endothelial cell disruption is essential to better understand BBB dynamics. Cortistatin is a neuroimmune mediator with anti-inflammatory and neuroprotective properties that exerts beneficial effects on the peripheral endothelium. However, its role in the healthy and injured brain endothelium remains to be evaluated. Herein, this study aimed to investigate the potential function of endogenous and therapeutic cortistatin in regulating brain endothelium dysfunction in a neuroinflammatory/neurodegenerative environment.MethodsWild-type and cortistatin-deficient murine brain endothelium and human cells were used for an in vitro barrier model, where a simulated ischemia-like environment was mimicked. Endothelial permeability, junction integrity, and immune response in the presence and absence of cortistatin were evaluated using different size tracers, immunofluorescence labelling, qPCR, and ELISA. Cortistatin molecular mechanisms underlying brain endothelium dynamics were assessed by RNA-sequencing analysis. Cortistatin role in BBB leakage was evaluated in adult mice injected with LPS.ResultsThe endogenous lack of cortistatin predisposes endothelium weakening with increased permeability, tight-junctions breakdown, and dysregulated immune activity. We demonstrated that both damaged and uninjured brain endothelial cells isolated from cortistatin-deficient mice, present a dysregulated and/or deactivated genetic programming. These pathways, related to basic physiology but also crucial for the repair after damage (e.g., extracellular matrix remodelling, angiogenesis, response to oxygen, signalling, and metabolites transport), are dysfunctional and make brain endothelial barrier lacking cortistatin non-responsive to any further injury. Treatment with cortistatin reversed in vitro hyperpermeability, tight-junctions disruption, inflammatory response, and reduced in vivo BBB leakage.ConclusionsThe neuropeptide cortistatin has a key role in the physiology of the cerebral microvasculature and its presence is crucial to develop a canonical balanced response to damage. The reparative effects of cortistatin in the brain endothelium were accompanied by the modulation of the immune function and the rescue of barrier integrity. Cortistatin-based therapies could emerge as a novel pleiotropic strategy to ameliorate neuroinflammatory/neurodegenerative disorders with disrupted BBB.
| S-EPMC10548650 | biostudies-literature
Project description:Although the nose, as a gateway for organism-environment interactions, may have a key role in asthmatic exacerbation, the rhinobiome of exacerbated children with asthma was widely neglected to date. Deep nasopharyngeal swab specimens, nasal epithelial spheroid cultures (NAEsp), and blood samples of acute exacerbated wheezers (WH), asthmatics (AB), and healthy controls (HC) were used for culture (n=146), 16 S-rRNA gene amplicon sequencing (n=64), proteomic and cytokine analyses. Interestingly, Proteobacteria were over-represented in WH (WH to AB: p=0.005; WH to HC: p=0.021), whereas Firmicutes and Bacterioidetes were associated with AB. In contrast, Actinobacteria commonly colonized HCs (PermANOVA p=0.005). Moreover, Staphylococcaceae (p<0.05), Enterobacteriaceae (p<0.05), Burkholderiaceae (p<0.05), Xanthobacteraceae (p<0.05), and Sphingomonadaceae (p<0.05) were significantly more abundant in AB compared to WH and HC. The α‐diversity analyses demonstrated an increase of bacterial abundance levels in atopic AB and a decrease in WH samples. Microbiome profiles of atopic WH differed significantly from atopic AB. The NAEsp bacterial exposure with M. catarrhalis, S. aureus and H. influenzae experiments provided a disrupted epithelial cell integrity, a cytokine release and cohort specific proteomic differences especially for M. catarrhalis cultures. Our comprehensive dataset contributes to a deeper insight into the poorly understood plasticity of the nasal microbiota, and, in particular, may enforce our understanding in the pathogenesis of asthma exacerbation in childhood.
2021-05-27 | PXD024694 | Pride
Project description:Endothelial ERK1/2 signaling maintains integrity of the quiescent endothelium
| PRJNA541240 | ENA
Project description:Angiogenesis plays a key role in tumor metastasis. Many genes may act in this process including formation of vessels, immune evasion,etc. Different gene expression profiles between lymphoma endothelium cells and reactive lymph node-derived endothelium cells may uncover these genes. And intensive mechanism researches on such key genes may explain the mechanisim of tumor-specific angiogenesis and help to explore effective treatment strategies to prevent/reverse tumor metastasis. We use microarrays to detail gene expression profiles of human lymphoma endothelium and reactive lymph node-derived endothelium. Lymph nodes were taken from surgery samples of cases pathologically diagnosed DLBCL (diffuse large B-cell lymphoma), PTL (peripheral T cell lymphoma) and reactive lymph nodes. The pure endothelium cells were isolated by LCM after immunohistochemical staining of CD34. We found Tim-3 was preferentially expressed on lymphoma-derived ECs via different expression profiles between lymphoma ECs and reactive lymph node-derived ECs. Intensive researches were carried out on Tim-3-expressing -ECs and we found that Tim-3 -expressing-Ecs may play important role on EC-mediated tumor evasion.
2010-01-14 | E-GEOD-19882 | biostudies-arrayexpress
Project description:Angiogenesis plays a key role in tumor metastasis. Many genes may act in this process including formation of vessels, immune evasion,etc. Different gene expression profiles between lymphoma endothelium cells and reactive lymph node-derived endothelium cells may uncover these genes. And intensive mechanism researches on such key genes may explain the mechanisim of tumor-specific angiogenesis and help to explore effective treatment strategies to prevent/reverse tumor metastasis. We use microarrays to detail gene expression profiles of human lymphoma endothelium and reactive lymph node-derived endothelium.
2010-01-14 | GSE19882 | GEO
Project description:Genome wide DNA methylation profiling of normal human corneal endothelium and human corneal endothelium from FECD cases. The Illumina Infinium MethylationEPIC 850K BeadChip was used to obtain DNA methylation profiles across approximately 850,000 CpGs in genomic DNA from human corneal endothelium samples. Samples included 11 non-FECD donors, 17 FECD cases.
2023-02-15 | GSE198917 | GEO
Project description:SARS-CoV-2 seriously injures human alveoli and causes severe respiratory illness. Histopathologic evidences suggested alveolar-capillary barrier integrity is compromised in COVID-19 deaths, however, little is known about how it is disrupted. In this study, we investigated the effects of SARS-CoV-2 infection on alveolar epithelium and pulmonary microvascular endothelium, and tried to elucidate the cross-talk between them during viral infection. Under monoculture system, SARS-CoV-2 infection caused massive virus replication and dramatic organelles re-modeling in alveolar epithelial cells. While, as for pulmonary microvascular endothelial cells, direct viral exposure had little effect on them, but treatment with culture supernatant from infected epithelial cellls significantly damaged them, which suggested SARS-CoV-2 affected endothelium indirectly, possibly by substances released from infected alveolar epithelium. Then, we tested SARS-CoV-2 infection in an alveolar epithelium/endothelium co-culture system, and found viral infection caused global proteomic modulations and ultrastructual changes in both cell types. Especially for alveolar epithelial cells, viral infection elicited significant protein changes and structural reorganizations across many sub-cellular compartments. Among the affected organelles, mitochondrion seems to be a primary target organelle. In addition, based on proteomic analysis and EM clues, we tested several autophagy inhibitors, and discovered one of them, Daurisoline, could inhibit virus replication effectively in cells. Collectively, our study revealed the distinctive responses of alveolar epithelium and microvascular endothelium to SARS-CoV-2 infection, which will expand our understanding of COVID-19 and helpful for targeted drug development.
2020-12-04 | PXD020470 | Pride
Project description:SARS-CoV-2 seriously injures human alveoli and causes severe respiratory illness. Histopathologic evidences suggested alveolar-capillary barrier integrity is compromised in COVID-19 deaths, however, little is known about how it is disrupted. In this study, we investigated the effects of SARS-CoV-2 infection on alveolar epithelium and pulmonary microvascular endothelium, and tried to elucidate the cross-talk between them during viral infection. Under monoculture system, SARS-CoV-2 infection caused massive virus replication and dramatic organelles re-modeling in alveolar epithelial cells. While, as for pulmonary microvascular endothelial cells, direct viral exposure had little effect on them, but treatment with culture supernatant from infected epithelial cells significantly damaged them, which suggested SARS-CoV-2 affected endothelium indirectly, possibly by substances released from infected alveolar epithelium. Then, we tested SARS-CoV-2 infection in an alveolar epithelium/endothelium co-culture system, and found viral infection caused global proteomic modulations and ultrastructural changes in both cell types. Especially for alveolar epithelial cells, viral infection elicited significant protein changes and structural reorganizations across many sub-cellular compartments. Among the affected organelles, mitochondrion seems to be a primary target organelle. In addition, based on proteomic analysis and EM clues, we tested several autophagy inhibitors, and discovered one of them, Daurisoline, could inhibit virus replication effectively in cells. Collectively, our study revealed the distinctive responses of alveolar epithelium and microvascular endothelium to SARS-CoV-2 infection, which will expand our understanding of COVID-19 and helpful for targeted drug development.
2021-11-11 | PXD029653 | Pride
Project description:Epigenome analysis of normal human corneal endothelium and corneal endothelium from FECD patients
| PRJNA817425 | ENA