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Project description:Genome-wide effect of ZBP1-mediated inflammatory response to LPS
| PRJNA801717 | ENA
Project description:Sepsis-induced acute lung injury (ALI), characterized by severe hypoxemia and pulmonary leakage, remains a leading cause of mortality in intensive care units. The exacerbation of ALI during sepsis is largely attributed to uncontrolled inflammatory responses and endothelial dysfunction. Emerging evidences suggest an important role of Z-DNA binding protein 1 (ZBP1) as a sensor in innate immune to drive inflammatory signaling and cell death during infections. However, the role of ZBP1 in sepsis-induced ALI has yet to be defined. We utilized ZBP1 knockout mice and combined single-cell RNA sequencing with experimental validation to investigate ZBP1's roles in the regulation of macrophages and lung endothelial cells during sepsis. We demonstrate that in sepsis, ZBP1 deficiency in macrophages reduces mitochondrial damage and inhibits glycolysis, thereby altering the metabolic status of macrophages. Consequently, this metabolic shift leads to a reduction in the differentiation of macrophages into pro-inflammatory states and decreases macrophage pyroptosis triggered by activation of the NLRP3 inflammasome. These changes significantly weaken the inflammatory signaling pathways between macrophages and endothelial cells, and alleviate endothelial dysfunction and cellular damage. These findings reveal important roles for ZBP1 in mediating multiple pathological processes involved in sepsis-induced ALI by modulating the functional states of macrophages and endothelial cells, thereby highlighting its potential as a promising therapeutic target.
2024-10-10 | GSE278767 | GEO
Project description:ZBP1/IMP1 is an mRNA binding protein that post-transcriptionally regulates the expression of a handful mRNAs, implicated in maintaining cell polarity and adhesion. We have previously shown that ZBP1 was able to inhibit proliferation and invasiveness of breast carcinoma cells in vitro. In the current study, we utilized orthotopic breast fat pad xenografts to further investigate the ZBP1-mediated functions in breast tumorigenesis and metastasis in vivo. We used microarrays to identify important gene for breast tumor growth and metastasis in response to ZBP1 expression Total RNA was extracted from breast tumor generated from ZBP1-expression and ZBP1-nonexpression MDA231 cells and used for hybridization on Affymetrix microarrays. We sought to obtain gene expression profiles from the individual tumors and identify what genes are up-regulated or down-regulated in the presence of ZBP1. The microarray experiments and data analysis were performed in 'Gene Company Limited' in Senzheng, China. G-10 and G-13, Tumors generated from MDA231/GFP cells; I-5 and I-6, tumors generated from MDA231/ZBP1-GFP cells.
2014-10-24 | E-GEOD-62638 | biostudies-arrayexpress
Project description:Cell death provides host defense and maintains homeostasis. Zα-containing molecules are essential for these processes. ZBP1 activates inflammatory cell death, PANoptosis, while ADAR1 serves as an RNA editor to maintain homeostasis. Here, we identify and characterize ADAR1’s interaction with ZBP1, defining its role in cell death regulation and tumorigenesis. Combining IFNs and nuclear export inhibitors (NEIs) activates ZBP1–dependent PANoptosis. ADAR1 suppresses PANoptosis by interacting with the Zα2 domain of ZBP1 to limit ZBP1 and RIPK3 interactions. Adar1fl/flLysMcre mice are resistant to development of colorectal cancer and melanoma, but deletion of the ZBP1 Zα2 domain restores tumorigenesis in these mice. In addition, treating wildtype mice with IFN-γ and the NEI KPT-330 regresses melanoma in a ZBP1–dependent manner. Our findings suggest that ADAR1 suppresses ZBP1–mediated PANoptosis, promoting tumorigenesis. Defining the functions of ADAR1 and ZBP1 in cell death is fundamental to inform therapeutic strategies for cancer and other diseases.
2021-10-19 | GSE184323 | GEO
Project description:B-cell lymphomas arising in Zbp1-/-Eu-Myc mice were compared to B-cell lymphomas arising in Zbp1+/+Eu-Myc mice
2014-04-01 | E-MTAB-2354 | biostudies-arrayexpress
Project description:ZBP1/IMP1 is an mRNA binding protein that post-transcriptionally regulates the expression of a handful mRNAs, implicated in maintaining cell polarity and adhesion. We have previously shown that ZBP1 was able to inhibit proliferation and invasiveness of breast carcinoma cells in vitro. In the current study, we utilized orthotopic breast fat pad xenografts to further investigate the ZBP1-mediated functions in breast tumorigenesis and metastasis in vivo. We used microarrays to identify important gene for breast tumor growth and metastasis in response to ZBP1 expression
2014-10-24 | GSE62638 | GEO
Project description:The innate immune system recognizes nucleic acids as a signature of microbial infection and initiates host-protective responses, including the production of type I IFN and proinflammatory cytokines. Z-DNA binding protein 1 (ZBP1, also known as DLM-1 or DAI) was previously identified as a dsDNA binding protein, triggering DNA-mediated activation of innate immune responses. However, mice or cells lacking ZBP1 produce normal levels of type I IFN in response to dsDNA. Therefore, the classification of ZBP1 as a true DNA sensor remains to be resolved. Here, we report that the single stranded RNA virus, influenza A virus (IAV) is a trigger of the cytosolic sensor ZBP1. Sensing of IAV infection by ZBP1 engages a novel NLRP3 inflammasome pathway that is not defined by the conventions of the canonical and non-canonical NLRP3 inflammasome pathways. Surprisingly, IAV-induced cell death was not prevented by the absence of the NLRP3 inflammasome. Instead, we identified parallel contributions from pyroptosis, necroptosis and apoptosis in the execution of ZBP1-dependent cell death, mediated by the kinase RIPK3. Overall, the ability of ZBP1 to sense IAV infection signifies a point of divergence for IAV-induced programmed cell death pathways and inflammasome activation. We used microarrays to explore the gene expression profiles differentially expressed in influenza-infected bone marrow derived macrophages (BMDM) isolated from Ifnar1-/- and wild-type mice.
2016-08-11 | E-GEOD-77611 | biostudies-arrayexpress
Project description:Lung cancer, a prevalent and aggressive disease, is characterized by recurrence and drug resistance. Understanding the underlying mechanisms and identifying new therapeutic targets are crucial for improving treatment outcomes. Our research indicates that methylation of cg09897064 and reduced expression of ZBP1 are associated with poor prognosis in lung cancer patients. Furthermore, these factors play a role in macrophage polarization, with ZBP1 upregulated in M1 macrophages compared to both M0 and M2 polarized macrophages. We observed cg09897064 methylation in M2 polarization, but not in M0 and M1 polarized macrophages. ATACseq analysis revealed closed chromatin accessibility of ZBP1 in M0 polarized macrophages, while open accessibility was observed in both M1 and M2 polarized macrophages. Our findings suggest that ZBP1 is downregulated in M0 polarized macrophages due to closed chromatin accessibility and downregulated in M2 polarized macrophages due to cg09897064 methylation. Further investigations manipulating cg09897064 methylation and ZBP1 expression through overexpression plasmids and shRNAs provided evidence for their role in modulating macrophage polarization and tumor growth. ZBP1 inhibits M2 polarization and suppresses tumor growth, while cg09897064 methylation promotes M2 polarization and macrophage-induced tumor growth. In mechanism investigations, we found that cg09897064 methylation impairs CEBPA binding to the ZBP1 promoter, leading to decreased ZBP1 expression. Targeting these factors may hold promise as a strategy for developing innovative checkpoint inhibitors in lung cancer treatment.
2024-01-01 | GSE245440 | GEO
Project description:The goal of this study was to compare the gene expression profiles of WT, Tfam+/-, Zbp1-/- and Tfam+/-Zbp1-/- MEFs.
2023-01-28 | GSE223553 | GEO
Project description:Macrophages Solvent, AA, LPS, AA+LPS
| PRJEB47005 | ENA