Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-43075
PROVIDER: PRJNA184347 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Monocyte chemoattractant protein 1 (MCP-1/CCL2) is critically involved in directing the migration of blood monocytes to sites of inflammation. Consequently, excessive MCP-1 secretion has been linked to many (auto)inflammatory diseases, whereas a lack of expression severely impairs immune responsiveness. We demonstrate that the atypical inhibitor of NF-κB ζ (IκBζ), a transcriptional co-activator required for the selective expression of a subset of NF-κB target genes, is a key activator of the Ccl2 gene. IκBζ-deficient macrophages exhibited impaired secretion of MCP-1 when challenged with diverse inflammatory stimuli, such as lipopolysaccharide or peptidoglycan. These findings were reflected at the level of Ccl2 gene expression, which was tightly coupled to the presence of IκBζ. Moreover, mechanistic insights acquired by chromatin immunoprecipitation demonstrate that IκBζ is directly recruited to the proximal promoter region of the Ccl2 gene and required for histone H3K9 trimethylation. Finally, IκBζ-deficient mice showed significantly impaired MCP-1 secretion and monocyte infiltration in an experimental model of peritonitis. Together, these findings suggest a distinguished role of IκBζ in mediating the targeted recruitment of monocytes in response to local inflammatory events. Peritoneal macrophages from Wildtype and IκBζ-Knockout mice were either stimulated with 1µg/ml LPS for 4h or left untreated (triplicates each)
2013-04-09 | E-GEOD-43075 | biostudies-arrayexpress
Project description:Monocyte chemoattractant protein 1 (MCP-1/CCL2) is critically involved in directing the migration of blood monocytes to sites of inflammation. Consequently, excessive MCP-1 secretion has been linked to many (auto)inflammatory diseases, whereas a lack of expression severely impairs immune responsiveness. We demonstrate that the atypical inhibitor of NF-κB ζ (IκBζ), a transcriptional co-activator required for the selective expression of a subset of NF-κB target genes, is a key activator of the Ccl2 gene. IκBζ-deficient macrophages exhibited impaired secretion of MCP-1 when challenged with diverse inflammatory stimuli, such as lipopolysaccharide or peptidoglycan. These findings were reflected at the level of Ccl2 gene expression, which was tightly coupled to the presence of IκBζ. Moreover, mechanistic insights acquired by chromatin immunoprecipitation demonstrate that IκBζ is directly recruited to the proximal promoter region of the Ccl2 gene and required for histone H3K9 trimethylation. Finally, IκBζ-deficient mice showed significantly impaired MCP-1 secretion and monocyte infiltration in an experimental model of peritonitis. Together, these findings suggest a distinguished role of IκBζ in mediating the targeted recruitment of monocytes in response to local inflammatory events.
2013-04-09 | GSE43075 | GEO
Project description:Inhibitor of NFκB ζ (IκBζ) is a transcriptional key regulator of monocyte chemoattractant protein-1 (MCP-1/CCL2)
2015-07-08 | E-GEOD-43075 | ExpressionAtlas
Project description:To identify the immunological status of the persistent and chronic stages, we analysed immunological genes in lung tissues from mice infected with M. tuberculosis. Based on the cDNA microarray results, 11 candidate cytokine genes, which were obviously up-regulated during the chronic stage compared with those during the persistent stage, were selected and clustered into three groups: 1) chemokine genes, except those of monocyte chemoattractant proteins (MCPs) (CXCL9, CXCL10, CXCL11, CCL5, CCL19); 2) MCP genes (CCL2, CCL7, CCL8, CCL12); and 3) TNF and IFN-γ genes. Results from the cDNA microarray and quantitative RT-PCR analyses revealed that the mRNA expression of the selected cytokine genes was significantly higher in lung tissues of the chronic stage than of the persistent stage. Three chemokines (CCL5, CCL19 and CXCL9) and three MCPs (CCL7, CCL2 and CCL12) were noticeably increased in the chronic stage compared with the persistent stage.
2017-04-15 | GSE97835 | GEO
Project description:Myeloid cells comprise the majority of immune cells in tumors, where their content and composition is not only driver mutation-specific, but also tumor type-dependent. While these cells are essential for shaping the tumor microenvironment, promoting tumor growth, and contributing to therapeutic resistance, targeting tumor-associated myeloid cells, including bone-marrow-derived monocytes and neutrophils, has not been successful. To eliminate monocyte recruitment, we employed CRISPR/Cas9-based methods to delete the region on murine chromosome 11 harboring the monocyte chemoattractant protein family (MCP) genes, Ccl2, Ccl7, Ccl8, Ccl12, and Ccl11, which we termed qMCP-KO. Using these qMCP-knockout mice in combination with genetically engineered mouse models (GEMM) of glioblastoma (GBM), we investigated myeloid infiltraion by sc-RNA seq. We found that when monocyte infiltraion was abolisehd, a compensatory influx of nuetrophil in these tumor occured. These neutrophil promote tumor growth by releasing TNF, contributing to tumor hypoxic responses and aggression.
2023-02-18 | GSE203154 | GEO
Project description:IκBζ, encoded by NFKBIZ, is a key transcriptional regulator in psoriasis, with a well-known role in keratinocytes but an unclear function in dermal fibroblasts. This study investigates cytokine-driven regulation of IκBζ in primary human dermal fibroblasts and integrates spatial transcriptomics to map NFKBIZ expression in psoriatic skin. Spatial transcriptomics (CosMx™) revealed expected expression of NFKBIZ in keratinocytes and additionally demonstrated elevated expression in dermal fibroblasts in lesional compared with non-lesional skin. Together, these findings identify IκBζ as an important regulator of inflammatory responses in dermal fibroblasts, broadening its established role in psoriasis pathogenesis.
2026-02-18 | GSE314158 | GEO
Project description:Enforced enhancement of H3K4me3 and H3K27ac, active chromatin marks, by inhibiting histone demethylases and deacetylases is positively linked with hard tissue formation by inducing matrix synthesis and osteo/odontogenic differentiation. However, the key endogenous epigenetic modifier of odontoblasts to regulate the expression of the genes coding dentin extracellular matrix (ECM) proteins has not been identified yet. We herein focused on IκBζ, which was originally identified as transcriptional regulator for NF-B and recently regarded as the local epigenetic modifier by independently on NF-B, and demonstrated that the IκBζ null mice exhibited thicker dentin width and narrower pulp chamber with aged mice having more drastic phenotypes. At 6 months old, dentin fluorescent labeling exhibited that dentin synthesis was significantly accelerated in the incisors of IκBζ null mice. In molars of IκBζ null mice, aggressive reactionary dentin adjacent to pulp horn was exhibited. Mechanistically, COL1A2 and COL1A1 collagen genes were increased in the odontoblasts rich fraction of IκBζ null mice than that of wild type in vivo and human odontoblasts-like cells transfected with siRNA for IκBζ than the control siRNA transfected cells in vitro. Further, the direct binding of IκBζ to COL1A2 promoter suppressed COL1A2 expression and the local active chromatin status marked with H3K4me3. By whole-genomic identification of H3K4me3 enrichments revealed that ECM and ECM organization-related gene loci were selectively activated by the knockdown of IκBζ, which consistently resulted in the up-regulation of these genes. Collectively, these results indicated that IκBζ is the key negative regulator of dentin formation in odontoblasts since the deletion of IκBζ expression enhanced dentin formation by inducing dentin ECM and ECM organization-related gene expression via altering the local chromatin status marked by H3K4me3. Therefore, IκBζ is a potential target for improving the clinical outcomes of dentin regeneration therapies such as pulp capping and pulp revitalization procedures.
2022-03-31 | GSE181596 | GEO
Project description:Skin repair is a complex, dynamic process involving multiple cell types. Using multiplex imaging, spatial transcriptomics, and single-cell RNA sequencing, we show that peripheral nerves —containing repair glia— form a pro-reparative niche closely interacting with macrophages and proliferating fibroblasts in acute skin wounds. Repair glia function as critical early-stage regulators of wound healing by initiating the inflammatory response throughsecretion of monocyte chemoattractant proteins, such as CCL2, which recruit monocyte derived macrophages. Accordingly, depletion of repair glia as well as glia-specific deletion of CCL2 reduces the number of macrophages, leading to impaired fibroblast proliferation and diminished fibroblast to myofibroblast transition. These findings position repair glia as a central component of the pro-reparative niche, coordinating the early immune response and orchestrating the temporal progression of wound healing.
2026-01-09 | GSE308952 | GEO
Project description:Skin repair is a complex, dynamic process involving multiple cell types. Using multiplex imaging, spatial transcriptomics, and single-cell RNA sequencing, we show that peripheral nerves —containing repair glia— form a pro-reparative niche closely interacting with macrophages and proliferating fibroblasts in acute skin wounds. Repair glia function as critical early-stage regulators of wound healing by initiating the inflammatory response throughsecretion of monocyte chemoattractant proteins, such as CCL2, which recruit monocyte derived macrophages. Accordingly, depletion of repair glia as well as glia-specific deletion of CCL2 reduces the number of macrophages, leading to impaired fibroblast proliferation and diminished fibroblast to myofibroblast transition. These findings position repair glia as a central component of the pro-reparative niche, coordinating the early immune response and orchestrating the temporal progression of wound healing.
2026-01-09 | GSE308799 | GEO
Project description:We found that 18-week administration of a prolyl hydroxylase inhibitor, enarodustat, improved glucose/lipid metabolism of BTBR ob/ob mice, which is a model of obesity and type 2 diabetes mellitus. Enarodustat-treated mice also exhibited reduced albuminuria along with ameliorated glomerular epithelial and endothelial damage. In order to elucidate the mechanism of renoprotection, we performed microarray gene expression analysis of isolated glomeruli. The initial screening process revealed 8965 probes whose absolute values of log2 (BTBR ob/ob mice treated with enarodustat/BTBR ob/ob mice treated with vehicle-only) exceeded 0.5. We then compared the expression levels of those 8965 probes between BTBR ob/ob and wild-type mice to identify molecules that were likely to be involved in the pathogenesis of glomerular injury. Such analysis revealed 71 genes which were significantly up-regulated and 47 genes which were significantly down-regulated in BTBR ob/ob mice compared to wild-type mice. The genes were ranked according to their fold-change values, and the analysis presented Ccl2/Mcp1 as the second-most up-regulated gene in BTBR ob/ob mice. The expression level of Ccl2/Mcp1 increased by 24.42-fold in BTBR ob/ob compared to wild-type mice, and its expression in enarodustat-treated BTBR ob/ob mice was decreased to 0.62 of the vehicle-only treated BTBR ob/ob mice. Urinary CCL2/MCP-1 was indeed decreased in enarodustat-treated BTBR ob/ob mice. In vitro experiments also showed that enarodustat suppressed palmitate-induced CCL2/MCP-1 production in murine mesangial cells. Taken together, enarodustat is likely to confer renoprotection through regulating the expression of CCL2/MCP-1 in the glomerulus.
2020-04-17 | GSE131266 | GEO