Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA290791 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The physiological function of the prion protein (PrP) has remained elusive despite its widely recognized role in neurodegenerative diseases and sustained efforts to understand its molecular biology. On the basis of its evolutionary relationship to ZIP zinc transporters, protein-protein interactions it engages in, and the characteristics of a gastrulation arrest phenotype in a PrP-deficient model, we considered that PrP may contribute to the morphogenetic reprogramming of cells underlying epithelial-to-mesenchymal (EMT) transitions. We have conducted three global proteomics analyses to (1) identify proteins whose levels are changed during EMT in wild-type NMuMG cells; and determine proteins whose levels are affected by (2) stable knockdown or (3) transient knockdown of the prion protein relative to levels observed in wild-type NMuMG cells. We observed a highly significant correlation between proteins, which are changed during EMT or following PrP knockdown.
2015-07-10 | PXD001875 | Pride
Project description:Glucocorticoid plays an essential role in various stress responses and metabolism, which is mediated by the glucocorticoid receptor (GR) in cells. This hormonal action is integrated to transcriptional control of the GR target genes in cell type-specific and condition-dependent manners. In this study, we report that GR regulates the angiopoietin-like 4 (ANGPTL4) gene in a CCCTC-binding factor (CTCF)-mediated chromatin context in human hepatic HepG2 cells. There were at least four CTCF-enriched sites and two GR-binding sites in the ANGPTL4 locus. Among them, major CTCF-enriched site was positioned nearly GR-bound enhancer of this gene. Using treatment with the synthetic glucocorticoid dexamethasone (Dex), our data showed that CTCF is required for proper induction and subsequent silencing of ANGPTL4 gene. Interestingly, this gene induction was diminished under the long-term Dex pretreatment. Although ANGPTL4 locus maintains stable higher-order chromatin conformation at the basal and the Dex-treated states, liganded GR activated the ANGPTL4 gene, but not the neighboring three genes, via the interactions between enhancer, promoter and CTCF sites. These results reveal that liganded GR spatiotemporally controls ANGPTL4 gene in the chromosomal context.
2017-01-10 | GSE85343 | GEO
Project description:To elucidate the mechanism by which Angiopoietin-like 4 (Angptl4) exerts a pro-proliferative effect on epidermal stem cells (EpSCs), we conducted RNA-seq analysis of EpSCs derived from 8-week-old Angptl4 gene knockout (KO) mice and wild-type (WT) control mice to gain a global view of the transcriptome profile regulated by ANGPTL4.
2024-11-20 | GSE282348 | GEO
Project description:Protracted inflammatory responses are signatures common to many gastrointestinal disorders. Severe and chronic disorders often bring about extensive tissue damage, in turn leading to hypercytokinemia. Here, we show that stimuli like dextran sulphate sodium salt (DSS) and stearic acid (SA) cause acute colonic inflammation, and ANGPTL4 is an important regulator in mediating the extent of colonic inflammation. Using comparative microarray gene expression analysis, we seek to identify genes whose expression are altered during inflammation between ANGPTL4+/+ and ANGPTL4-/- mice.
2017-03-28 | GSE78500 | GEO
Project description:Renal cell carcinoma (RCC), the most common form of kidney cancer, is a heterogeneous disease with clear cell RCC (ccRCC) being the most prevalent and aggressive subtype. While most ccRCC tumors have elevated expression of angiopoietin-like 4 (ANGPTL4), in our study we identified a significant subset of patients whose cancers show no increase in ANGPTL4 expression. These patients have a worse prognosis compared to the patients with high expression of ANGPTL4. These ANGPTL4-low cancers are characterized by the increased frequency of wild-type Von Hippel-Lindau (wt VHL), a gene that is commonly mutated in ccRCC, and an enrichment for genes associated with lipid metabolism. Using RCC tumor models with wild type VHL, we demonstrate that ANGPTL4 behaves as a tumor suppressor. The loss of ANGPTL4 in ccRCC cell lines results in increased tumor growth and colony formation in a lysosomal acid lipase (LAL)-dependent manner, a phenotype rescued by the expression of N-terminus ANGPTL4. At the mechanistic level, the loss of ANGPTL4 increases lysosomal acid lipase activity in ccRCC cells. This data suggests that ANGPTL4 enacts its tumor-suppressive effects in ccRCC by regulating LAL activity. Importantly, the identified patient cohort with low ANGPTL4 expression may exhibit increased reliance on lipid metabolism, which can be a point of target for future therapy.
2024-07-30 | GSE273236 | GEO
Project description:Specificity protein 1 (SP1) is an essential transcription factor regulating multiple cancer-related genes. Since aberrant expression of SP1 was known to be related to cancer development and progression, we focused on SP1 expression in gastric carcinoma and its correlation with disease outcomes. We discovered a different relationship between SP1 expression and patient survival in intestinal- and diffuse-type gastric cancer. In diffuse-type gastric cancer, patient survival decreased as SP1 expression increased (P < 0.05) in accordance with previously published papers, whereas the lack of SP1 expression in intestinal-type gastric cancer was correlated significantly with poor survival (P < 0.05). When SP1 downregulation was forced in high SP1 expressor intestinal-type gastric cell line MKN28 with siRNA, both migration and invasion were increased but cell proliferation was decreased. In accordance with these results, microarray data in siRNA-transfected MKN28 showed that genes inhibiting migration were downregulated and the expression of genes negatively facilitating proliferation was increased. Both migration and invasion, however, in low SP1 expressor intestinal-type gastric cell line AGS were decreased by forced SP1 expression. In contrast to intestinal-type, in diffuse-type gastric cell line SNU484, high SP1 expressor, both migration and invasion were decreased by siRNA. Contrary to previous studies, which did not reflect differences between the 2 histological types, our results showed that low expression of SP1 is involved in cancer progression and metastasis, and has a different effect on intestinal-type compared to diffuse-type gastric adenocarcinoma. 2 samples for MKN28 cells: si-SP1 against si-control and dyeswap of it upon 72 hour
2012-01-01 | E-GEOD-34792 | biostudies-arrayexpress
Project description:Comparative expression data between ANGPTL4+/+ and ANGPTL4-/- mice whole colon tissue during DSS or SA-induced inflammation.
| PRJNA313144 | ENA
Project description:<p>Renal fibrosis, a hallmark of chronic kidney diseases, is driven by the activation of renal fibroblasts. Recent studies have highlighted the role of glycolysis in this process. Nevertheless, one critical glycolytic activator, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), remains unexplored in renal fibrosis. Upon reanalyzing the single-cell sequencing data from Dr. Humphreys' lab, we noticed an upregulation of glycolysis, gluconeogenesis, and TGFβ signaling pathway in myofibroblasts from fibrotic kidneys after unilateral ureter obstruction (UUO) or kidney ischemia/reperfusion. Furthermore, our experiments showed significant induction of PFKFB3 in mouse kidneys following UUO or kidney ischemia/reperfusion. To delve deeper into the role of PFKFB3, we generated mice with Pfkfb3 deficiency specifically in myofibroblasts (Pfkfb3f/fPostnMCM). Following UUO or kidney ischemia/reperfusion, a substantial decrease of fibrosis in injured kidneys of Pfkfb3f/fPostnMCM mice was identified compared to their wild-type littermates. Additionally, in cultured renal fibroblast NRK-49F cells, PFKFB3 was elevated upon exposure to TGFβ1, accompanied by the increase of α-SMA and fibronectin. Notably, this upregulation was significantly diminished with PFKFB3 knockdown, correlated with a glycolysis suppression. Mechanistically, the glycolytic metabolite lactate promoted the fibrotic activation of NRK-49F. In conclusion, our study demonstrates the critical role of PFKFB3 in driving fibroblast activation and subsequent renal fibrosis.</p>
2024-03-12 | MTBLS8281 | MetaboLights
Project description:Angiopoietin-like protein 4 (ANGPTL4, also referred to as Fiaf) has been proposed as circulating mediator between the gut microbiota and fat storage in adipose tissue. Very little is known about mechanisms of regulation of ANGPTL4 in the colon. Here we show that transcription and subsequent secretion of ANGPTL4 in human T84 and HT-29 colonocytes is highly induced by physiological concentrations of products of bacterial fermentation, the short chain fatty acids (SCFA). Induction of ANGPTL4 by SCFA cannot be mimicked by the histone deacetylase inhibitor Trichostatin A. SCFA induce ANGPTL4 by activating the nuclear receptor PPARγ, as shown by use of PPARγ antagonist, PPARγ knock-down, and transactivation assay, which shows activation of PPARγ but not PPARα and PPARδ. At concentrations required for PPARγ activation and ANGPTL4 induction in colonocytes, SCFA do not stimulate PPARγ in mouse 3T3-L1 and human SGBS adipocytes, suggesting that SCFA act as selective PPARγ modulators (SPPARM), which is supported by coactivator peptide recruitment assay and structural modelling. Consistent with the notion that fermentation leads to PPAR activation in vivo, feeding mice a diet rich in inulin was associated with induction of PPAR target genes and pathways in the colon, as shown by microarray and subsequent gene set enrichment analysis. It can be concluded that 1) SCFA potently stimulate ANGPTL4 synthesis in human colonocytes; 2) SCFA transactivate and bind to PPARγ by serving as selective PPAR modulators. Our data point to activation of PPARγ as a novel mechanism of gene regulation by SCFA in the colon.
2013-03-11 | GSE43065 | GEO
Project description:We performed genome-wide expression profiling analysis to define the genes underlying the synthetic-lethal relationship between CBP and p300. We extracted 1,936 genes whose expression levels changed >2-fold upon p300-knockdown (KD) in CBP-KO cells, or upon CBP-KD in p300-KO cells, but not in either KD in wild-type cells
2015-12-12 | GSE73682 | GEO