Similar Datasets
Project description:Loss of ZNF750 increased the inflammatory gene expression of differentiated human keratinocytes treated with POLY IC
2024-08-28 | GSE248486 | GEO
Project description:ARID1A plays an important role in skin inflammation.
| PRJNA966998 | ENA
Project description:ZNF750 plays an important role in skin inflammation induced by POLY IC treatment
| PRJNA1044110 | ENA
Project description:Cigarette smoke (CS), the major cause of chronic obstructive pulmonary disease, contains a variety of oxidative components that were implicated in the regulation of Src homology domain 2-containing protein tyrosine phosphatase 2 (Shp2) activity. However, the contribution of Shp2 enzyme to chronic obstructive pulmonary disease pathogenesis remains unclear. We investigated the role of Shp2 enzyme in blockading CS-induced pulmonary inflammation. Shp2 levels were assessed in vivo and in vitro. Mice (C57BL/6) or pulmonary epithelial cells (NCI-H292) were exposed to CS or cigarette smoke extract (CSE) to induce acute injury and inflammation. Lungs of smoking mice showed increased levels of Shp2, compared with those of controls. Treatment of lung epithelial cells with CSE showed elevated levels of Shp2 associated with the increased release of IL-8. Selective inhibition or knockdown of Shp2 resulted in decreased IL-8 release in response to CSE treatment in pulmonary epithelial cells. In comparison with CS-exposed wild-type mice, selective inhibition or conditional knockout of Shp2 in lung epithelia reduced IL-8 release and pulmonary inflammation in CS-exposed mice. In vitro biochemical data correlate CSE-mediated IL-8 release with Shp2-regulated epidermal growth factor receptor/Grb-2-associated binders/MAPK signaling. Our data suggest an important role for Shp2 in the pathological alteration associated with CS-mediated inflammation. Shp2 may be a potential target for therapeutic intervention for inflammation in CS-induced pulmonary diseases.
| S-EPMC3496208 | biostudies-literature
Project description:It has become increasingly important to understand how retinal inflammation is regulated because inflammation plays a role in retinal degenerative diseases. Lipocalin 2 (LCN2), an acute stress response protein with multiple innate immune functions, is increased in ATP-binding cassette subfamily A member 4 (Abca4) -/- retinol dehydrogenase 8 (Rdh8) -/- double-knockout mice, an animal model for Stargardt disease and age-related macular degeneration (AMD). To examine roles of LCN2 in retinal inflammation and degeneration, Lcn2-/-Abca4-/-Rdh8-/- triple-knockout mice were generated. Exacerbated inflammation following light exposure was observed in Lcn2-/-Abca4-/-Rdh8-/- mice as compared with Abca4-/-Rdh8-/- mice, with upregulation of proinflammatory genes and microglial activation. RNA array analyses revealed an increase in immune response molecules such as Ccl8, Ccl2, and Cxcl10 To further probe a possible regulatory role for LCN2 in retinal inflammation, we examined the in vitro effects of LCN2 on NF-κB signaling in human retinal pigmented epithelial (RPE) cells differentiated from induced pluripotent stem cells derived from healthy donors. We found that LCN2 induced expression of antioxidant enzymes heme oxygenase 1 and superoxide dismutase 2 in these RPE cells and could inhibit the cytotoxic effects of H2O2 and LPS. ELISA revealed increased LCN2 levels in plasma of patients with Stargardt disease, retinitis pigmentosa, and age-related macular degeneration as compared with healthy controls. Finally, overexpression of LCN2 in RPE cells displayed protection from cell death. Overall these results suggest that LCN2 is involved in prosurvival responses during cell stress and plays an important role in regulating inflammation during retinal degeneration.
| S-EPMC5916038 | biostudies-literature
Project description:Dysregulation and abnormal expression of inflammatory mediators by keratinocytes promote the pathogenesis of the skin inflammation such as allergic contact dermatitis (ACD). High-mobility group box 1 (HMGB1) protein, a prototypical damage-associated molecular pattern (DAMP), that is expressed in the nucleus but released extracellularly upon inflammation has gained attention as an accelerator for skin inflammation. However, in vivo role of HMGB1 in ACD and other skin disorders remains to be elusive. In this study, we generated conditional knockout mice in which HMGB1 is deleted in keratinocytes and examined its role in skin inflammation models including 2,4-dinitrofluorobenezene (DNFB)-induced ACD. Unexpectedly, deletion of HMGB1 in keratinocytes exacerbated skin inflammation, accompanied by increased ear thickening. Elevated mRNA expression of interleukin-24 (IL-24), a known cytokine which promotes the pathogenesis of ACD, was also observed in the skin lesion of the mice. In accordance with above observations, both constitutive and IL-4-induced Il24 mRNA expression in vitro was augmented in hmgb1-deficient primary mouse keratinocytes and keratinocyte cell line PAM212 cells. Chromatin immunoprecipitation (ChIP) analysis revealed increased binding of tri-methyl histone H3 (lys4) (H3K4me3), a well-known histone mark for transcription active genes, to the promoter region of the Il24 gene in the hmgb1-deficient cells. ChIP-sequencing data also showed broad changes of H3K4me3 mark in the cells. Thus, HMGB1 in the nucleus dictates histone modifications. In conclusion, our study demonstrated a key role for HMGB1 in keratinocytes in the maintenance of chromatin modification status to protect from exuberant skin inflammation.
2021-01-01 | GSE159695 | GEO
Project description:The study identifies genes that are regulated by the loss of the chromatin remodeller subunit ARID1A in colorectal cancer cell lines. This gene is frequently mutated in colorectal cancer.
2019-06-11 | E-MTAB-7791 | biostudies-arrayexpress
Project description:Arid1a is the subunit of SWI/SNF complex, which was reported to guide SWI/SNF to DNA. Here, we found that loss of Arid1a in the liver and other adult tissues results in improved organ regeneration. Within SWI/SNF complexes, Arid1a physically interacts with C/ebpα, a hepatocyte transcription factor that drives maturation and limits proliferation. Genome-wide analysis showed that loss of Arid1a reduces the recruitment and activity of C/ebpα on target promoters, resulting in expression programs that favor regeneration and cellular fitness during injury. Arid1a binding is enriched in promoters near transcriptional start sites (TSSs), and C/ebpα binds at precisely the same positions, indicating that Arid1a facilitates C/ebpα binding across the genome. Perfuse and isolate primary hepatocytes from mice livers, analysis of genomic occupancy of C/ebpα and H3K4me2 in hepatocytes from Arid1a WT and Arid1a liver specific KO mice by ChIP-seq. Analysis of genomic occupancy of Arid1a in the hepatocytes from V5-Arid1a transgenic mouse by ChIP-seq.
2016-03-30 | E-GEOD-65167 | biostudies-arrayexpress
Project description:ARID1A, an epigentic modifier, is often mutated in ovarian clear cell carcinoma (OCCC). In addition, EZH2 is frequently upregulated in OCCC. Inhibtion of EZH2 with an inhibitor (GSK126) selectively inhibits ARID1A-mutated cells. This study was designed to understand changes in gene expression profiles following EZH2 inhibition or ARID1A restoration. Chromatin remodelers such as ARID1A are frequently mutated in a broad array of cancers. However, targeted cancer therapy based on ARID1A mutation status has not been described. Intriguingly, ARID1A mutated cancers typically lack genomic instability, suggesting significant involvement of epigenetic mechanisms. Here we show that inhibition of the EZH2 methyltransferase acts in a synthetic lethal manner in ARID1A mutated cells. Remarkably, ARID1A mutation status correlated with response to EZH2 inhibitor. Genome-wide profiling revealed antagonistic roles of ARID1A and EZH2 in gene regulation. Further, we identified PIK3IP1 as a direct ARID1A/EZH2 target gene whose upregulation contributes to the observed synthetic lethality in the EZH2 inhibitor treated ARID1A mutated cells. Significantly, EZH2 inhibitor caused the regression of established ARID1A mutated tumors in vivo. Together, this data demonstrate a synthetic lethality between ARID1A mutation and EZH2 inhibition. They indicate that pharmacological inhibition of EZH2 represents a novel treatment strategy for ARID1A mutated cancers.
2015-01-20 | E-GEOD-54979 | biostudies-arrayexpress
Project description:A nonsense mutation in ARID1A was identified by next generation sequencing in non-dysplastic Barrett's esophagus [BE] tissue and esophageal adenocarcinoma [EAC] tissue of a patient diagnosed with EAC. Immunohistochemistry performed on an independent archival cohort demonstrated ARID1A protein loss in 0% (0/76), 4.9% (2/40), 14.3% (4/28), 16.0% (8/50), and 12.2% (12/98) of normal squamous epithelium, BE, low-, high-grade dysplasia, and EAC tissues, respectively. Enhanced cell growth, proliferation and invasion were observed upon ARID1A knockdown in EAC cells. ARID1A was knocked down in OE33 cells (Sample MS_1 and MS_3) using on-TARGET smartpool ARID1A siRNA. At the same time, OE33 cells were transfected with a non-targeting siRNA, and these experiments (Samples MS_2 and MS_4) functioned as mock controls. Cells were harvested after 48 hours and total RNA was extracted using the Rneasy kit (Qiagen) Aim Affymetrix Human PrimeView Gene Expression Array : to determine the downstream effectors of ARID1A that are likely to contribute to the oncogenic phenotype caused by ARID1A down-regulation. Two biological replicates of each condition (2x ARID1A knockdown, and 2x Mock) were used for the microarray experiment.
2012-05-31 | E-GEOD-38380 | biostudies-arrayexpress