Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Microglia aggravate white matter injury via C3/C3aR pathway after experimental subrachnoid hemorrhage

ABSTRACT: Microglia aggravate white matter injury via C3/C3aR pathway after experimental subrachnoid hemorrhage

PROVIDER: PRJNA1069737 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR27744360_1.fastq.gz	Fastqsanger.gz
	SRR27744360_2.fastq.gz	Fastqsanger.gz
	SRR27744361_1.fastq.gz	Fastqsanger.gz
	SRR27744361_2.fastq.gz	Fastqsanger.gz
	SRR27744362_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 24

Similar Datasets

Microglia aggravate white matter injury via C3/C3aR pathway after experimental subrachnoid hemorrhage

Project description:Activation of microglia induces neuroinflammation in acute and chronic phase is closely related to the white matter injury (WMI) pathophysiologyafter subrachnoid hemorrhage (SAH). The complement C3a receptor (C3aR) has a dual role in regulating inflammation and plays a role in neurodevelopment, neuroplasticity and neurodegeneration, but it’s effect on WMI during SAH re'mairemains unknown. In this study, 175 male C57BL/6J mice received SAH by endovascular perforation. oxy-Hb was used to simulate SAH in vitro. Multiple technical approaches, including immunohistochemistry, transcriptome sequencing, neurological function assessment, and various molecular biotechnologies, were used to assess the activation of the C3-C3aR pathway after SAH and its effects on microglial polarizations and WMI after SAH. The results showed that abnormal microglial activation after SAH was accompanied by upregulation of complement C3 and C3aR. C3aR inhibition reduced abnormal microglial activation, attenuated neuroinflammation, ameliorated WMI and cognitive deficits after SAH. RNA-Seq revealed that C3aR inhibition downregulated several immune and inflammatory pathways and ameliorated cellular injury by downregulating Pidd1 expression. The adverse effects of C3-C3aR in SAH may be related to Endoplasmic reticulum (ER) stress-dependent cellular injury and formation of inflammasome. PERK agonists exacerbate cellular injury and neuroinflammation attenuated by C3aR inhibition. Intranasal C3a treatment during the subacute phase of SAH helps to reduce astrocyte reactivity and ameliorate cognitive deficits after SAH. In conclusion, these findings suggest that C3aR plays a critical role in the regulation of neuroinflammation and WMI after SAH, providing new therapeutic targets to ameliorate WMI and cognitive deficits after SAH.

2025-01-25 | GSE254320 | GEO

mRNA profiles of tumor infiltrating macrophage and monocyte derived from C3 wild-type and knock-out mice, subjected to sarcoma transplantable model

Project description:Complement has emerged as a component of tumor promoting inflammation. We conducted a systematic assessment of the role of complement activation and effector pathways in sarcomas. C3-/-, MBL1/2-/- and C4-/- mice showed reduced susceptibility to 3-methylcholanthrene sarcomagenesis and transplanted sarcomas, whereas C1q and factor B deficiency had marginal effects. Complement 3a receptor (C3aR), but not C5aR1 and C5aR2, deficiency mirrored the phenotype of C3-/- mice. C3 and C3aR deficiency were associated with reduced accumulation and functional skewing of tumor-associated macrophages, increased T cell activation and response to anti-PD-1 therapy. Transcriptional profiling of sarcoma infiltrating macrophages and monocytes revealed the enrichment of MHC II-dependent antigen presentation pathway in C3-deficient cells. In patients, C3aR expression correlated with a macrophage population signature and C3 deficiency-associated signatures predicted better clinical outcome. These results suggest that the lectin pathway and C3a/C3aR axis are key components of complement and macrophage-mediated sarcoma promotion and immunosuppression.

2020-11-24 | GSE141692 | GEO

Lung epithelial cell-derived C3 protects against pneumonia-induced lung injury

Project description:The complement component C3 is a fundamental plasma protein for host defense, produced largely by the liver. However, recent work has demonstrated the critical importance of tissue-specific C3 expression in cell survival. Here we analyzed the effects of local versus peripheral sources of C3 expression in a model of bacterial pneumonia. While mice with global C3 deficiency had severe pneumonia-induced lung injury, those deficient in liver-deficient C3 remain protected, comparable to wildtype mice. Human lung transcriptome analysis showed that secretory epithelial cells, such as club cells, are a major source of C3. Mice with a tamoxifen-induced C3 gene ablation from club cells in the lung had worse pulmonary injury compared to similarly treated controls, despite maintaining normal circulating C3 levels. Finally, in human cellular and mouse pneumonia models, we show that C3 reduces epithelial cell death mediated through the alternative pathway component Factor B, rather than the C3aR. Thus, our findings suggest that a locally-derived C3-Factor B pathway protects the lung mucosal barrier.

2023-02-03 | GSE218554 | GEO

Intracellular activation of complement C3 leads to PD-L1 antibody treatment resistance via modulating tumor-associated macrophages

Project description:Mounting evidence has highlighted the importance of complement in the construction of an immunosuppressive tumor microenvironment (TME). Tumor cell-derived C3 has been previously reported, however, whether and how it acts on anti-tumor immunity remains to be elucidated. Here, we describe a unique role of tumor cell-derived C3 in suppressing anti-tumor immunity. Tumor cell-derived C3 was activated intracellularly, which results in generation of C3a. C3a could modulate tumor-associated macrophages (TAMs) via C3a-C3aR-PI3Kγ signaling, thereby repressing anti-tumor immunity. More importantly, deletion of C3 in tumor cells with high C3 expression is sufficient to enhance the efficacy of ɑPD-L1 treatment. Collectively, our present results suggest tumor cell-derived C3 may serve as a novel target in cancer immunotherapy, specifically targeting C3 in tumor cells to enhance anti-tumor immunity.

2018-09-21 | GSE120274 | GEO

Development of gene expression signatures in experimental intracerebral hemorrhage

Project description:To identify the potential lncRNA and mRNA post intracerebral hemorrhage (ICH), we have employed lncRNA microarray expression profiling. 570 mRNAs and 313 lncRNAs were identified in the ICH vs sham group .Expression of six mRNA (Saa3, Col10a1, Mmp13, Oxt, Pcdhb6 and Resp18) and lncRNA (ENSMUT00000141700, AK143011, ENSMUT00000128306, AK030988, ENSMUST00000187076 and ENSMUST00000134129) from this signature was quantified by qPCR.

2023-05-17 | GSE227683 | GEO

Humanized C3 Mouse: A Novel Accelerated Model of C3 Glomerulopathy

Project description:We developed a novel, rapidly-progressing, severe murine model of C3G by replacing the mouse C3 gene with the human C3 homologue using Velocigene® technology. We conducted functional, histological, molecular and pharmacologic assays to characterize the presentation of renal disease and useful pharmacologic interventions in the humanized C3 (C3hu/hu) mice.

2020-05-20 | GSE150838 | GEO

Paraburkholderia sp. C3 strain:C3

Project description:Paraburkholderia sp. C3 strain:C3 Genome sequencing

| PRJNA684679 | ENA

Pantoea sp. C3 strain:C3

Project description:Pantoea sp. C3 strain:C3 Genome sequencing

| PRJNA1170070 | ENA

Transcriptome profiling of rat brain samples in two age groups in responding to intracerebral hemorrhage

Project description:Aging-induced decline of endogenous neuroprotection has been shown to aggravate intracerebral hemorrhage (ICH)-induced acute brain injury, however, the underlying mechanisms in brain are still little known. In this study, we applied a rat ICH model to study the transcriptional responses in the early and late aging (13-month and 22-month old) rats that show substantial differences in brain damage and recovery. Transcriptome analysis (RNA-seq) reveals that brain expression of neuroinflammation genes is similarly and selectively upregulated in ICH, which includes genes in the cellular response to interferon gamma function. We show that the anti-IFN-γ treatment effectively reduces ICH-induced acute brain injury.

2020-04-27 | GSE149317 | GEO

Development of Specific Therapy Against Right Ventricular Failure

Project description:Right ventricular (RV) failure plays a critical role in any type of heart failure. However, there is no specific therapy developed for RV failure. To understand RV failure, we focused on the RV specific genes. Global gene expression analysis showed that alternative complement pathway-related genes including C3 and Cfd were significantly upregulated in right ventricle in murine heart. We generated the RV failure by right ventricle-specific pressure overload model mice, pulmonary artery constriction (PAC), which induces RV failure around 14 days. In C3 knockout (C3KO) mice, PAC-induced RV dysfunction and fibrosis were significantly attenuated. C3a is produced from C3 by C3 convertase complex including Cfd. Cfd knockout mice also attenuated PAC-induced RV failure. Moreover, C3a receptor (C3aR) antagonist dramatically improved PAC-induced RV dysfunction in wild type mice. Here we revealed the crucial role of C3-Cfd-C3a-C3aR axis in RV failure and highlight the potential therapeutic target for RV failure with no pharmacologic option.

2021-09-07 | GSE183504 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data