Mus musculus
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ABSTRACT:
PROVIDER: PRJNA241309 | ENA |
REPOSITORIES: ENA
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Project description:To investigate the detailed molecular mechanisms for the regulatory role of HIF-1α in colon, microarray gene expression analysis was performed on colon RNA isolated from 6- to 8-week-old Hif-1α+/+, Hif-1αLSL/LSL mice. Background & Aims: The progression and growth of solid tumors leads to a state where tumors outgrow their capacity for efficient oxygenation and nutrient uptake and an increase in tumor hypoxia. Tumor hypoxic response is mediated by hypoxia-inducible factor (HIF)-1a and HIF-2a. These transcription factors regulate a battery of genes that are critical for tumor oxygenation, tumor metabolism, and cell proliferation and survival. Therefore, inhibitors of HIF have been sought for as anti-neoplastic agents in several different kinds of cancers. Interestingly, in ischemic and inflammatory diseases of the intestine, activation of HIF-1a is beneficial, and can reduce intestinal inflammation. The efficacy of pharmacological agents that chronically activate HIF-1a are decreased due to the tumorigenic potential of HIF. However, recent advance in understanding HIF signaling have identified mechanisms, which could allow for isoform specific activators. Activation of HIF-2a increases colon carcinogenesis and progression in mouse models. However, the role of chronic HIF-1a activation is unclear in the progression in colon cancer. The present data demonstrates that activation of HIF-1a in epithelial cells does not increase colon carcinogens or progression in two mouse models of colon cancer, and provides the proof of principle that HIF-1a activation maybe safe as therapies for inflammatory bowel disease. Global gene expression profiling in colon RNAs isolated from 6- to 8-week-old Hif-1α+/+ (n=5, Shah 019) and Hif-1αLSL/LSL (n=5, Shah 020).
2014-05-14 | E-GEOD-55915 | biostudies-arrayexpress
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:Gene Expression profiles of colon from Hif-2αF/F, Hif-2αlΔIE treated with DSS
| PRJNA186026 | ENA
Project description:To investigate the detailed molecular mechanisms for the regulatory role of HIF-1α in colon, microarray gene expression analysis was performed on colon RNA isolated from 6- to 8-week-old Hif-1α+/+, Hif-1αLSL/LSL mice. Background & Aims: The progression and growth of solid tumors leads to a state where tumors outgrow their capacity for efficient oxygenation and nutrient uptake and an increase in tumor hypoxia. Tumor hypoxic response is mediated by hypoxia-inducible factor (HIF)-1a and HIF-2a. These transcription factors regulate a battery of genes that are critical for tumor oxygenation, tumor metabolism, and cell proliferation and survival. Therefore, inhibitors of HIF have been sought for as anti-neoplastic agents in several different kinds of cancers. Interestingly, in ischemic and inflammatory diseases of the intestine, activation of HIF-1a is beneficial, and can reduce intestinal inflammation. The efficacy of pharmacological agents that chronically activate HIF-1a are decreased due to the tumorigenic potential of HIF. However, recent advance in understanding HIF signaling have identified mechanisms, which could allow for isoform specific activators. Activation of HIF-2a increases colon carcinogenesis and progression in mouse models. However, the role of chronic HIF-1a activation is unclear in the progression in colon cancer. The present data demonstrates that activation of HIF-1a in epithelial cells does not increase colon carcinogens or progression in two mouse models of colon cancer, and provides the proof of principle that HIF-1a activation maybe safe as therapies for inflammatory bowel disease.
2014-05-14 | GSE55915 | GEO
Project description:Hypoxia inducible factor-1α (HIF-1α) is a critical transcription factor for the hypoxic response, angiogenesis, normal hematopoietic stem cell regulation, and cancer development. Importantly, HIF-1α is also a key regulator for immune cell activation. In order to determine whether HIF-1α is sufficient for developing MDS phenotypes, we generated blood specific inducible HIF-1α transgenic mice. Using Vav1-Cre/Rosa26-loxP-Stop-loxP (LSL) rtTA driver, stable HIF-1α can be induced in a doxycycline administration dependent manner. After induction, HIF-1α-induced mice developed thrombocytopenia, leukocytopenia, macrocytic anemia, and multi-lineage dysplasia. We also found activation of both innate and adaptive immunity in HIF-1α- induced mice compared to those from control mice. Taken together, these data suggest that HIF-1α is sufficient to trigger a variety of key MDS features
2018-12-25 | GSE83988 | GEO
Project description:To describe the protein profile in hippocampus, colon and ileum tissue’ changing after the old faeces transplants, we adopted a quantitative label free proteomics approach.
2021-09-09 | PXD016432 | Pride
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: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 3, 6, 12 and 24 hours.
2015-07-24 | E-GEOD-59729 | biostudies-arrayexpress
Project description:Hypoxia-inducible factor 1 (HIF-1) activates the transcription of genes encoding proteins that enable cells to adapt to reduced O2 availability. HIF-1 controls physiological processes that are dysregulated in cancer and heart disease, including angiogenesis, energy metabolism, and immunity. These disease processes are also characterized by increased activation of adenosine and β-adrenergic receptors, which triggers the synthesis of cyclic adenosine monophosphate (cAMP), the allosteric regulator of cAMP-dependent protein kinase A (PKA). We performed a proteomic screen in cardiomyocytes and identified PKA as a HIF-1α-interacting protein. PKA interacted with HIF-1α and phosphorylated Thr63 and Ser692 in vitro, coimmunoprecipitated with HIF-1α from cell lysates, and enhanced HIF transcriptional activity and target gene expression in human HeLa cells and rat cardiomyocytes. PKA inhibited the proteasomal degradation of HIF-1α in an O2-independent manner that required phosphorylation of Thr63 and Ser692 and was not affected by mutation of Pro402 and Pro564. PKA also stimulated the binding of the coactivator p300 to HIF- 1α to enhance its transcriptional activity and this effect was lost upon mutation of Asn803. These data establish a potential link between stimuli that increase cAMP concentrations and HIF-1α-dependent changes in gene expression, which contribute to the pathophysiology of cancer and heart disease.
2016-06-07 | PXD003795 | Pride
Project description:To investigate the detailed molecular mechanisms for the regulatory role of HIF-2α in experimental colitis, microarray gene expression analysis was performed on colon RNA isolated from 6- to 8-week-old Hif-2αF/F, Hif-2αlΔIE mice treated with 3%DSS for 3 days. Background & Aims: Hypoxic inflammation is characterized by decreased oxygen tension in inflammatory foci, and is a notable feature in inflammatory bowel disease (IBD). Hypoxic response is mediated by transcription factors hypoxia-inducible factor (HIF)-1α and HIF-2α, both of which are highly induced in IBD. HIF-1α is a protective factor that limits intestinal barrier dysfunction during inflammation. However, the role of HIF-2α has not been assessed in hypoxic inflammation and IBD. Methods: A hypoxia reporter mouse model was used to test the presence of hypoxia and HIF-2α in dextran sulfate sodium (DSS) and Citrobacter rodentium (C.rod)-induced colitis. The role of HIF-2α in these mouse models of colitis was further assessed in mice with an intestinal epithelium-specific gain- and loss-of-function of HIF-2α. Results: Induction of hypoxia and HIF-2α was confirmed in both murine experimental colitis models and human IBD samples. Disruption of HIF-2α attenuated colonic inflammation whereas stabilization of HIF-2α potentiated inflammation in mouse models of colitis. Interestingly, intestine specific overexpression of HIF-2α but not HIF-1α leads to spontaneous colitis and premature death in mice. Further mechanistic analysis showed that HIF-2α is a driver for pro-inflammatory response and is critical regulator of intestinal epithelial-derived tumor necrosis factor (TNF)-α. Blocking TNF-α completely ameliorated HIF-2α potentiated intestinal inflammation. Conclusions: These data demonstrate that HIF-2α is a critical transcription factor essential in intestinal epithelium elicited inflammatory response. Global gene expression profiling in colon RNAs isolated from 7-week-old Hif-2αF/F (n=6, Shah 007) and Hif-2αΔIE (n=5, Shah 008).
2013-02-28 | E-GEOD-43416 | biostudies-arrayexpress