Intestine epithelial specific hypoxia-inducible factor-1α overexpression on ileum transcriptome
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PROVIDER: PRJNA1177978 | ENA |
REPOSITORIES: ENA
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Project description:Background: Intestine epithelial hypoxia-inducible factor-1α (HIF-1α) plays a critical role in maintaining gut barrier function. The aim of this study was to determine genetic activation of intestinal HIF-1α ameliorates western diet-induced metabolic dysfunction–associated steatotic liver disease (MASLD). Methods: Male and/or female intestinal epithelial-specific Hif1α overexpression mice (Hif1α LSL/LSL;VilERcre) and wild-type littermates (Hif1α LSL/LSL) were fed with regular chow diet, high fructose (HFr) or high-fat (60% Kcal) high-fructose diet (HFHFr) for 8 weeks. Metabolic phenotypes were profiled. Results: Male Hif1α LSL/LSL;VilERcre mice exhibited markedly improved glucose tolerance compared to Hif1α LSL/LSL mice in response to HFr diet. Eight weeks HFHFr feeding led to obesity in both Hif1α LSL/LSL;VilERcre and Hif1α LSL/LSL mice. However, male Hif1α LSL/LSL;VilERcre mice exhibited markedly attenuated hepatic steatosis along with reduced liver size and liver weight compared to male Hif1α LSL/LSL mice. Moreover, HFHFr-induced systemic inflammatory responses were mitigated in male Hif1α LSL/LSL;VilERcre mice compared to male Hif1α LSL/LSL mice and those responses were not evident in female mice. Ileum RNA-seq analysis revealed that glycolysis/gluconeogenesis was up in male Hif1α LSL/LSL;VilERcre mice accompanied by increased epithelial cell proliferation. Conclusion: Our data provide evidence that genetic activation of intestinal HIF-1α markedly ameliorates western diet-induced MASLD in a sex-dependent manner. The underlying mechanism is likely attributed to HIF-1α activation induced upregulation of glycolysis, which, in turn, leading to enhanced epithelial cell proliferation and augmented gut barrier function.
2024-10-26 | GSE280362 | GEO
Project description:GATA6 is a transcription factor involved in the differentiation of intestinal epithelial cells into differentiated absorptive epithelial cells. GATA6 is expressed in all segments of the small intestine. We examined the impact of deleting GATA6 from intestinal epithelial cells of the adult ileum
2011-06-07 | GSE22416 | GEO
Project description:Injured peripheral neurons successfully activate a pro-regenerative transcriptional program to enable axon regeneration and functional recovery. How transcriptional regulators coordinate the expression of such programs remains unclear. Here we show that hypoxia-inducible factor 1α (HIF-1α) controls multiple injury-induced genes in sensory neurons and contribute to the pre-conditioning lesion effect. Knockdown of HIF-1α in vitro or conditional knockout in vivo impairs sensory axon regeneration. The HIF-1α target gene Vascular Endothelial Growth Factor A (VEGFA) is expressed in injured neurons and contributes to stimulate axon regeneration. Induction of HIF-1α using hypoxia enhances axon regeneration in vitro and in vivo in sensory neurons. Hypoxia also stimulates motor neuron regeneration and accelerates neuromuscular junction reinnervation. This study demonstrates that HIF-1α represents a critical transcriptional regulator in regenerating neurons and suggests hypoxia as a tool to stimulate axon regeneration.
2016-01-21 | GSE73415 | GEO
Project description:Hypoxia inducible factor-1 (HIF-1) is a central transcriptional regulator of genes associated with adaptive responses to hypoxia. NPM1 is a histone chaperone found to associate with HIF-1α in a phosphorylation dependent manner and increase its activty. The aim of this study was to find if HIF-1α and NPM1 regualate gene expression under hypoxia. Transcriptome analysis using Quant-RNA-seq after HIF-1α or NPM1 silencing under hypoxia reveals a significant number of genes, the hypoxic expression of which depends on both proteins.
2021-12-15 | GSE158890 | GEO
Project description:Ammonia is a toxic by-product of metabolism that causes cellular stress. Although a number of proteins are involved in adaptive stress response, specific factors that counteract ammonia-induced cellular stress and regulate cell metabolism that facilitate survival against toxicity have yet to be identified. We demonstrated that hypoxia-inducible factor-1α (HIF-1α) is stabilised and activated by ammonia stress. HIF-1α activated by ammonium chloride compromises ammonia-induced apoptosis. Furthermore, we identified glutamine synthetase (GS) as a key driver of cancer cell proliferation and glutamine-dependent metabolism under ammonia stress in ovarian cancer stem-like cells expressing CD90. Interestingly, activated HIF-1α counteracts glutamine synthetase function in glutamine metabolism by facilitating glycolysis and elevating glucose dependency. Our studies reveal the hitherto unknown functions of HIF-1α in biphasic ammonia stress management in cancer stem-like cells. GS facilitates proliferation and HIF-1α contributes to metabolic remodelling in cellular energy usage resulting in attenuated proliferation but conversely promoting cell survival.
2017-11-22 | GSE107251 | GEO
Project description:GATA6 is a transcription factor involved in the differentiation of intestinal epithelial cells into differentiated absorptive epithelial cells. GATA6 is expressed in all segments of the small intestine. We examined the impact of deleting GATA6 from intestinal epithelial cells of the adult ileum 6-8 week old Villin-CreERT2 mice or Villin-CreERT2 mice crossed to GATA6 flox/flox mice were treated with a single injection of tamoxifen. (100 mg/ml) for 5 consecutive days. 28 days later the ileum was dissected and RNA prepared from the whole ileal segment using the RNAeasy method with DNAse treatment. Three individual mice were examined in each of the control and GATA6 KO groups.
2011-06-07 | E-GEOD-22416 | biostudies-arrayexpress
Project description:Analysis of Huh-7 hepatocarcinoma cell line depleted of NDRG3 or HIF-1α under hypoxic condition. HIF-1α and NDRG3 have distinct functions in hypoxia responses. Results provide insight into molecular basis of HIF-independent signaling in the development and progression of hypoxic tumors Gene expression profiles of Huh-7 cells stably expressing NDRG3-shRNA or HIF-1α-shRNA under normoxia were compared to gene expression profiles of Huh-7 stable cells under hypoxia for 6, 12 and 24 hours.
2015-07-24 | E-GEOD-55212 | biostudies-arrayexpress
Project description:Hypoxia-inducible factor 1 (HIF-1) is a transcriptional regulator that mediates cellular adaptive responses to hypoxia. Hypoxia-inducible factor 1α (HIF-1α) is involved in the development of ascites syndrome (AS) in broiler chickens. Therefore, studying the effect of HIF-1α on the cellular transcriptome under hypoxic conditions will help to better understand the mechanism of HIF-1α in the development of AS in broilers. In this study, we analyzed the gene expression profile of the DF-1 cell line under hypoxic conditions by RNA-seq. Additionally, we constructed the HIF-1α knockdown DF-1 cell line by using the RNAi method and analyzed the gene expression profile under hypoxic conditions. The results showed that exposure to hypoxia for 48 hours had a significant impact on the expression of genes in the DF-1 cell line, which related to cell proliferation, stress response, and apoptosis. In addition, after HIF-1α knockdown more differential expression genes appeared than in wild-type cells, and the expression of most hypoxia-related genes was either down-regulated or remained unchanged. Pathway analysis results showed that differentially expressed genes were mainly enriched in pathways related to cell proliferation, apoptosis, and oxidative phosphorylation. Our study obtained transcriptomic data from chicken fibroblasts at different hypoxic times and identified the potential regulatory network associated with HIF-1α. This data provides valuable support for understanding the transcriptional regulatory mechanism of HIF-1α in the development of AS in broilers.
2023-11-15 | GSE244260 | GEO
Project description:We herein found the strong expression of hypoxia-inducible factor-1α (HIF-1α) in tuberculosis granulomas and more rapid death of HIF-1α-conditional knockout mice than wild-type mice after M. tuberculosis infection. These results prompted us to investigate the role of HIF-1α in host defenses against infection. Bone-marrow derived macrophages from Wild-type (WT) mice and HIF-1α-conditional knockout (HIF-1 CKO) mice were infected with M tuberculosis H37Rv (multiplicity of infection = 0.5) for 12 h, and extracellular bacilli were removed from the macrophage culture medium. Cells were cultured for 4 days in the presence of 500 U/ml IFN-γ. In microarray analysis using Gene Chip Mouse Gene 1.0 ST Array, the expression of 757 and 1190 genes was ≥1.3-fold stronger and ≥0.77-fold weaker, respectively, in HIF-1 CKO than in WT.
2018-09-30 | E-MTAB-7244 | biostudies-arrayexpress
Project description:Increased levels of hypoxia and hypoxia inducible factor 1α (HIF-1α) in human sarcomas correlate with tumor progression and radiation resistance. Prolonged anti-angiogenic therapy of tumors can delay tumor growth but may also increase hypoxia and HIF-1α activity. In our recent clinical trial, treatment with the anti-vascular endothelial growth factor A (VEGF-A) antibody, bevacizumab, followed by a combination of bevacizumab and radiation led to near complete necrosis in nearly half of sarcomas. Gene set enrichment analysis of microarrays from pre-treatment biopsies found the Gene Ontology category “Response to hypoxia” was upregulated in poor responders, and hierarchical clustering based on 140 hypoxia-responsive genes separated poor responders from good responders. The most commonly used chemotherapeutic drug for sarcomas, doxorubicin (Dox), was recently found to block HIF-1α binding to DNA at low metronomic doses. We thus examined Dox treatment in 4 sarcoma cell lines, and found Dox at low concentrations (1-10 uM) blocked HIF-1α induction of VEGF-A by 84-97%, while inhibition of other HIF-1α-target genes including CA9, c-Met and FOXM1 was variable. HT1080 sarcoma xenografts had increased hypoxia and/or HIF-1α activity with increasing tumor size and with anti-VEGF receptor antibody (DC101) treatment. Combining DC101 and metronomic Dox had a synergistic effect in suppressing growth of HT1080 xenografts, primarily via induction of tumor endothelial cell apoptosis. In conclusion, sarcomas respond to increased hypoxia by expressing HIF-1α-target genes which may promote resistance to anti-angiogenic and other therapies. Metronomic Dox can block HIF-1α activation of target genes and works synergistically with anti-VEGF therapy to inhibit sarcomas. Pre-treatment biopsies were collected from 16 human sarcoma. The gene expression analysis was performed using Illumina platform.
2011-08-29 | E-GEOD-31715 | biostudies-arrayexpress