121 results match your criteria hif2α

gain-of-function mutation modulates the stiffness of smooth muscle cells and compromises vascular mechanics.

iScience 2021 Apr 2;24(4):102246. Epub 2021 Mar 2.

Department of Chemical and Biomolecular Engineering and Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.

Heterozygous gain-of-function (GOF) mutations of hypoxia-inducible factor 2α (HIF2A), a key hypoxia-sensing regulator, are associated with erythrocytosis, thrombosis, and vascular complications that account for morbidity and mortality of patients. We demonstrated that the vascular pathology of HIF2A GOF mutations is independent of erythrocytosis. We generated HIF2A GOF-induced pluripotent stem cells (iPSCs) and differentiated them into endothelial cells (ECs) and smooth muscle cells (SMCs). Read More

View Article and Full-Text PDF

Experimental modulation of Interleukin 1 shows its key role in chronic kidney disease progression and anemia.

Sci Rep 2021 Mar 18;11(1):6288. Epub 2021 Mar 18.

Institute of Nephrology, Schneider Children's Medical Center of Israel, 14 Kaplan Street, 4920235, Petach Tikva, Israel.

Inflammation in chronic kidney disease (CKD) is mostly due to activation of the innate immune system, in which Interleukin-1 (IL-1) is a key player. Anemia of CKD may also be due to erythropoietin (EPO) resistance, clinically associated with inflammation. IL-1 receptor antagonist knockout (RaKO) mice show arthritis and excessive inflammation. Read More

View Article and Full-Text PDF

LncIHAT Is Induced by Hypoxia-Inducible Factor 1 and Promotes Breast Cancer Progression.

Mol Cancer Res 2021 Apr 30;19(4):678-687. Epub 2020 Dec 30.

Department of Pathology, UT Southwestern Medical Center, Dallas, Texas.

Hypoxia induces thousands of mRNAs and miRNAs to mediate tumor malignancy. However, hypoxia-induced long noncoding RNA (lncRNA) transcriptome and their role in triple-negative breast cancer (TNBC) have not been defined. Here we identified hypoxia-induced lncRNA transcriptome in two human TNBC cell lines by whole transcriptome sequencing. Read More

View Article and Full-Text PDF

Long non-coding RNA ZFAS1 promotes the expression of EPAS1 in gastric cardia adenocarcinoma.

J Adv Res 2021 Feb 24;28:7-15. Epub 2020 Jun 24.

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, PR China.

LncRNA (Long non-coding RNA) ZFAS1 (zinc finger antisense 1) functions as the oncogene in multiple cancers, including gastric cancer. However, its function and underlying mechanism in the GCA (gastric cardia adenocarcinoma), the most aggressive type of gastric cancer, remain unknown. We demonstrated here that the LncRNA ZFAS1 was up-regulated in GCA tissues. Read More

View Article and Full-Text PDF
February 2021

Differential Contribution of N- and C-Terminal Regions of HIF1α and HIF2α to Their Target Gene Selectivity.

Int J Mol Sci 2020 Dec 10;21(24). Epub 2020 Dec 10.

Research Unit, Hospital Santa Cristina, Research Institute Princesa (IP), Autonomous University of Madrid, 28009 Madrid, Spain.

Cellular response to hypoxia is controlled by the hypoxia-inducible transcription factors HIF1α and HIF2α. Some genes are preferentially induced by HIF1α or HIF2α, as has been explored in some cell models and for particular sets of genes. Here we have extended this analysis to other HIF-dependent genes using in vitro WT8 renal carcinoma cells and in vivo conditional -deficient mice models. Read More

View Article and Full-Text PDF
December 2020

Transmembrane Prolyl 4-Hydroxylase is a Novel Regulator of Calcium Signaling in Astrocytes.

eNeuro 2021 Jan-Feb;8(1). Epub 2021 Jan 8.

Oulu Center for Cell-Matrix Research, Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu 90014, Finland

Prolyl 4-hydroxylases (P4Hs) have vital roles in regulating collagen synthesis and hypoxia response. A transmembrane P4H (P4H-TM) is a recently identified member of the family. Biallelic loss of function P4H-TM mutations cause a severe autosomal recessive intellectual disability syndrome in humans, but functions of P4H-TM are essentially unknown at cellular level. Read More

View Article and Full-Text PDF
January 2021

Hypoxia Alters the Response to Anti-EGFR Therapy by Regulating EGFR Expression and Downstream Signaling in a DNA Methylation-Specific and HIF-Dependent Manner.

Cancer Res 2020 11 6;80(22):4998-5010. Epub 2020 Oct 6.

Breast & Ovarian Cancer Program, Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Intratumoral hypoxia occurs in 90% of solid tumors and is associated with a poor prognosis for patients. Cancer cells respond to hypoxic microenvironments by activating the transcription factors, hypoxia-inducible factor 1 (HIF1) and HIF2. Here, we studied the unique gene expression patterns of 31 different breast cancer cell lines exposed to hypoxic conditions. Read More

View Article and Full-Text PDF
November 2020

Targeting the HIF2-VEGF axis in renal cell carcinoma.

Nat Med 2020 10 5;26(10):1519-1530. Epub 2020 Oct 5.

Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Insights into the role of the tumor suppressor pVHL in oxygen sensing motivated the testing of drugs that target the transcription factor HIF or HIF-responsive growth factors, such as VEGF, for the treatment of cancers caused by VHL inactivation, such as clear-cell renal cell carcinoma (ccRCC). Multiple VEGF inhibitors are now approved for the treatment of ccRCC, and a HIF2α inhibitor has advanced to phase 3 development for this disease. These inhibitors are now also increasingly combined with immune-checkpoint blockers. Read More

View Article and Full-Text PDF
October 2020

Inactivation of HIF-prolyl 4-hydroxylases 1, 2 and 3 in NG2-expressing cells induces HIF2-mediated neurovascular expansion independent of erythropoietin.

Acta Physiol (Oxf) 2021 01 22;231(1):e13547. Epub 2020 Sep 22.

Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.

Aim: NG2 cells in the brain are comprised of pericytes and NG2 glia and play an important role in the execution of cerebral hypoxia responses, including the induction of erythropoietin (EPO) in pericytes. Oxygen-dependent angiogenic responses are regulated by hypoxia-inducible factor (HIF), the activity of which is controlled by prolyl 4-hydroxylase domain (PHD) dioxygenases and the von Hippel-Lindau (VHL) tumour suppressor. However, the role of NG2 cells in HIF-regulated cerebral vascular homeostasis is incompletely understood. Read More

View Article and Full-Text PDF
January 2021

Neuroprotective Effect of HIF Prolyl Hydroxylase Inhibition in an In Vitro Hypoxia Model.

Antioxidants (Basel) 2020 Jul 24;9(8). Epub 2020 Jul 24.

Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603950 Nizhny Novgorod, Russia.

A novel potent analog of the branched tail oxyquinoline group of hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors, neuradapt, has been studied in two treatment regimes in an in vitro hypoxia model on murine primary hippocampal cultures. Neuradapt activates the expression of HIF1 and HIF2 target genes and shows no toxicity up to 20 μM, which is more than an order of magnitude higher than its biologically active concentration. Cell viability, functional activity, and network connectivity between the elements of neuronal networks have been studied using a pairwise correlation analysis of the intracellular calcium fluctuations in the individual cells. Read More

View Article and Full-Text PDF

CHD4 Promotes Breast Cancer Progression as a Coactivator of Hypoxia-Inducible Factors.

Cancer Res 2020 09 22;80(18):3880-3891. Epub 2020 Jul 22.

Department of Pathology, UT Southwestern Medical Center, Dallas, Texas.

Recruitment of RNA polymerase II to hypoxia-inducible factor (HIF) target genes under normoxia is a prerequisite for HIF-mediated transactivation. However, the underlying mechanism of this recruitment remains unknown. Here we report that chromodomain helicase DNA-binding protein 4 (CHD4) physically interacts with α and β subunits of HIF1 and HIF2 and enhances HIF-driven transcriptional programs to promote breast cancer progression. Read More

View Article and Full-Text PDF
September 2020

HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: Metastatic pheochromocytomas and paragangliomas: proceedings of the MEN2019 workshop.

Endocr Relat Cancer 2020 08;27(8):T41-T52

Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.

Pheochromocytomas and paragangliomas (PPGLs) are adrenal or extra-adrenal autonomous nervous system-derived tumors. Most PPGLs are benign, but approximately 15% progress with metastases (mPPGLs). mPPGLs are more likely to occur in patients with large pheochromocytomas, sympathetic paragangliomas, and norepinephrine-secreting tumors. Read More

View Article and Full-Text PDF

The Expression of Decidual Protein Induced by Progesterone (DEPP) is Controlled by Three Distal Consensus Hypoxia Responsive Element (HRE) in Hypoxic Retinal Epithelial Cells.

Genes (Basel) 2020 01 18;11(1). Epub 2020 Jan 18.

Department of Ophthalmology, Lab for Retinal Cell Biology, University of Zurich, 8952 Schlieren, Switzerland.

Hypoxia affects the development and/or progression of several retinopathies. Decidual protein induced by progesterone () has been identified as a hypoxia-responsive gene that may be part of cellular pathways such as autophagy and connected to retinal diseases. To increase our understanding of regulation in the eye, we defined its expression pattern in mouse and human retina and retinal pigment epithelium (RPE). Read More

View Article and Full-Text PDF
January 2020

HIF2-Induced Long Noncoding RNA RAB11B-AS1 Promotes Hypoxia-Mediated Angiogenesis and Breast Cancer Metastasis.

Cancer Res 2020 03 3;80(5):964-975. Epub 2020 Jan 3.

Department of Pathology, UT Southwestern Medical Center, Dallas, Texas.

Hypoxia induces a vast array of long noncoding RNAs (lncRNA) in breast cancer cells, but their biological functions remain largely unknown. Here, we identified a hitherto uncharacterized hypoxia-induced lncRNA RAB11B-AS1 in breast cancer cells. RAB11B-AS1 is a natural lncRNA upregulated in human breast cancer and its expression is induced by hypoxia-inducible factor 2 (HIF2), but not HIF1, in response to hypoxia. Read More

View Article and Full-Text PDF

HIF1/2-exerted control over glycolytic gene expression is not functionally relevant for glycolysis in human leukemic stem/progenitor cells.

Cancer Metab 2019 27;7:11. Epub 2019 Dec 27.

Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen, 9700RB The Netherlands.

Background: Hypoxia-inducible factors (HIF)1 and 2 are transcription factors that regulate the homeostatic response to low oxygen conditions. Since data related to the importance of HIF1 and 2 in hematopoietic stem and progenitors is conflicting, we investigated the chromatin binding profiles of HIF1 and HIF2 and linked that to transcriptional networks and the cellular metabolic state.

Methods: Genome-wide ChIPseq and ChIP-PCR experiments were performed to identify HIF1 and HIF2 binding sites in human acute myeloid leukemia (AML) cells and healthy CD34 hematopoietic stem/progenitor cells. Read More

View Article and Full-Text PDF
December 2019

Roles of HIF1 and HIF2 in pulmonary hypertension: it all depends on the context.

Eur Respir J 2019 12 12;54(6). Epub 2019 Dec 12.

Dept of Pediatrics, Northwestern University Feinberg School of Medicine, Anne and Robert H. Lurie Children's Hospital, Chicago, IL, USA

View Article and Full-Text PDF
December 2019

Sustain, Adapt, and Overcome-Hypoxia Associated Changes in the Progression of Lymphatic Neoplasia.

Front Oncol 2019 21;9:1277. Epub 2019 Nov 21.

Department of Pathology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

Irregular perfusion and related tissue hypoxia is a common feature of solid tumors the role of which in the survival and progression cancer has been gradually recognized. Adaptation and selection mechanisms in hypoxic areas in solid tumors are regulated by Hypoxia Inducible transcriptional factor 1 (HIF1) and other hypoxia mediators and are associated with aggressive clinical behavior in a large spectrum of malignancies. Aggressive forms of lymphatic neoplasias present with solid tumor-like features, also including rapid cell growth, necrosis and angiogenesis, the clinical potential of which is still underestimated. Read More

View Article and Full-Text PDF
November 2019

Hif1a and Hif2a can be safely inactivated in cone photoreceptors.

Sci Rep 2019 11 6;9(1):16121. Epub 2019 Nov 6.

Lab for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Schlieren, CH-8952, Switzerland.

Impaired tissue oxygenation results in hypoxia and leads to the activation of hypoxia-inducible transcription factors (HIF). A chronic, HIF-triggered molecular response to hypoxia may be an important factor in the etiology of age-related macular degeneration (AMD) and is likely activated before any clinical manifestation of the disease. Thus, HIF1 and HIF2 recently emerged as potential therapeutic targets for AMD. Read More

View Article and Full-Text PDF
November 2019

Stabilization of myeloid-derived HIFs promotes vascular regeneration in retinal ischemia.

Angiogenesis 2020 05 3;23(2):83-90. Epub 2019 Oct 3.

Division of Genetics, UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK.

The retinal vasculature is tightly organized in a structure that provides for the high metabolic demand of neurons while minimizing interference with incident light. The adverse impact of retinal vascular insufficiency is mitigated by adaptive vascular regeneration but exacerbated by pathological neovascularization. Aberrant growth of neovessels in the retina is responsible for impairment of sight in common blinding disorders including retinopathy of prematurity, proliferative diabetic retinopathy, and age-related macular degeneration. Read More

View Article and Full-Text PDF

Tuftelin and HIFs expression in osteogenesis.

Histochem Cell Biol 2019 Nov 13;152(5):355-363. Epub 2019 Sep 13.

Laboratory of Odontogenesis and Osteogenesis, Institute of Animal Physiology and Genetics, v.v.i, Academy of Sciences of the Czech Republic, Veveri 97, Brno, Czech Republic.

Tuftelin was originally discovered and mostly studied in the tooth, but later found also in other organs. Despite its wide distribution among tissues, tuftelin's function has so far been specified only in the formation of enamel crystals. Nevertheless, in many cases, tuftelin was suggested to be associated with cellular adaptation to hypoxia and recently even with cell differentiation. Read More

View Article and Full-Text PDF
November 2019

Suppression of HIF2 signalling attenuates the initiation of hypoxia-induced pulmonary hypertension.

Eur Respir J 2019 12 12;54(6). Epub 2019 Dec 12.

Cardiovascular Pulmonary Research Laboratories, Division of Pulmonary Sciences and Critical Care Medicine, Division of Pediatrics-Critical Care, Depts of Medicine and Pediatrics, University of Colorado, Aurora, CO, USA

Most published studies addressing the role of hypoxia inducible factors (HIFs) in hypoxia-induced pulmonary hypertension development employ models that may not recapitulate the clinical setting, including the use of animals with pre-existing lung/vascular defects secondary to embryonic HIF ablation or activation. Furthermore, critical questions including how and when HIF signalling contributes to hypoxia-induced pulmonary hypertension remain unanswered.Normal adult rodents in which global HIF1 or HIF2 was inhibited by inducible gene deletion or pharmacological inhibition (antisense oligonucleotides (ASO) and small molecule inhibitors) were exposed to short-term (4 days) or chronic (4-5 weeks) hypoxia. Read More

View Article and Full-Text PDF
December 2019

Glutathione peroxidase 3 (GPX3) suppresses the growth of melanoma cells through reactive oxygen species (ROS)-dependent stabilization of hypoxia-inducible factor 1-α and 2-α.

J Cell Biochem 2019 11 16;120(11):19124-19136. Epub 2019 Jul 16.

Department of Biochemistry and Molecular Biology, Kunming Medical University, Kunming, Yunnan, PR China.

In this study, we aimed to explore the mechanism of glutathione peroxidase 3 (GPX3) in the growth of malignant melanoma (MM) cells by hypoxia-inducible factor-1α (HIF1-α) and HIF2-α regulating the metabolism through reactive oxygen species (ROS). The messenger RNA and protein expression of GPX3, HIF1-α, HIF2-α in tissues, and cell lines were measured by reverse transcription-quantitative PCR and Western blot analysis. A375 cells were transfected with GPX3 overexpression plasmid, small interfering RNA (siRNA) targeting GPX3, or siRNA targeting HIF1-α/HIF2-α to upregulate or downregulate the expression of GPX3 or HIF1-α/HIF2-α. Read More

View Article and Full-Text PDF
November 2019

Dysregulation of proangiogeneic factors in pressure-overload left-ventricular hypertrophy results in inadequate capillary growth.

Ther Adv Cardiovasc Dis 2019 Jan-Dec;13:1753944719841795

Center of Molecular Medicine Cologne, University of Cologne, Cologne, Germany.

Background: Pressure-overload left-ventricular hypertrophy (LVH) is an increasingly prevalent pathological condition of the myocardial muscle and an independent risk factor for a variety of cardiac diseases. We investigated changes in expression levels of proangiogeneic genes in a small animal model of LVH.

Methods: Myocardial hypertrophy was induced by transaortic constriction (TAC) in C57BL/6 mice and compared with sham-operated controls. Read More

View Article and Full-Text PDF

Algorithmic evaluation of hereditary erythrocytosis: Pathways and caveats.

Int J Lab Hematol 2019 May;41 Suppl 1:89-94

Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.

Multiple algorithms have been published for the evaluation of hereditary erythrocytosis (HE). Typical entry points begin after excluding the more common acquired conditions through investigations of clinical history and assessment of cardiac, pulmonary, or vascular system disorders. Prior exclusion of JAK2 mutations, particularly the common JAK2 V617F mutation, is indicated in adults but less so in pediatric populations. Read More

View Article and Full-Text PDF

Selective EGLN Inhibition Enables Ablative Radiotherapy and Improves Survival in Unresectable Pancreatic Cancer.

Cancer Res 2019 05;79(9):2327-2338

Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

When pancreatic cancer cannot be removed surgically, patients frequently experience morbidity and death from progression of their primary tumor. Radiation therapy (RT) cannot yet substitute for an operation because radiation causes fatal bleeding and ulceration of the nearby stomach and intestines before achieving tumor control. There are no FDA-approved medications that prevent or reduce radiation-induced gastrointestinal injury. Read More

View Article and Full-Text PDF

LncRNA HIF2PUT inhibited osteosarcoma stem cells proliferation, migration and invasion by regulating HIF2 expression.

Artif Cells Nanomed Biotechnol 2019 Dec;47(1):1342-1348

c Department of Emergency , the First Hospital, Jilin University , Changchun , China.

Purpose: The function of lncRNAs in cancer stem cells (CSCs) remains to be elucidated. The present study aimed to investigate the regulating role of a novel lncRNA, hypoxia-inducible factor-2α (HIF-2α) promoter upstream transcript (HIF2PUT), in osteosarcoma stem cells.

Methods: The expression of lncRNA HIF2PUT and HIF-2α in osteosarcoma stem cell lines and tissues was monitored by real-time PCR and western blot. Read More

View Article and Full-Text PDF
December 2019

A humanized bone microenvironment uncovers HIF2 alpha as a latent marker for osteosarcoma.

Acta Biomater 2019 04 2;89:372-381. Epub 2019 Mar 2.

Queensland University of Technology (QUT), 60 Musk Avenue, Kelvin Grove, QLD 4059, Brisbane, Australia. Electronic address:

The quest for predictive tumor markers for osteosarcoma (OS) has not well progressed over the last two decades due to a lack of preclinical models. The aim of this study was to investigate if microenvironmental modifications in an original humanized in vivo model alter the expression of OS tumor markers. Human bone micro-chips and bone marrow, harvested during hip arthroplasty, were implanted at the flanks of NOD/scid mice. Read More

View Article and Full-Text PDF

Hypoxia-inducible factor 2α is a negative regulator of osteoblastogenesis and bone mass accrual.

Bone Res 2019 21;7. Epub 2019 Feb 21.

1Department of Orthopaedic Surgery, School of Medicine, University of Michigan, Ann Arbor, MI USA.

Osteoblasts, which are the bone-forming cells, operate in a hypoxic environment. The transcription factors hypoxia-inducible factor-1α (HIF1) and HIF2 are key mediators of the cellular response to hypoxia. Both are expressed in osteoblasts. Read More

View Article and Full-Text PDF
February 2019

HIF-1α and HIF-2α Differently Regulate the Radiation Sensitivity of NSCLC Cells.

Cells 2019 01 12;8(1). Epub 2019 Jan 12.

Department of Radiotherapy (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University, 6229 ET Maastricht, The Netherlands.

The hypoxia-inducible transcription factors (HIF)-1/2α are the main oxygen sensors which regulate the adaptation to intratumoral hypoxia. The aim of this study was to assess the role of the HIF proteins in regulating the radiation response of a non-small cell lung cancer (NSCLC) in vitro model. To directly assess the unique and overlapping functions of HIF-1α and HIF-2α, we use CRISPR gene-editing to generate isogenic H1299 non-small cell lung carcinoma cells lacking HIF-1α, HIF-2α or both. Read More

View Article and Full-Text PDF
January 2019

Development of extracellular matrix supported 3D culture of renal cancer cells and renal cancer stem cells.

Cytotechnology 2019 Feb 31;71(1):149-163. Epub 2018 Dec 31.

Department of Oncology, Military Institute of Medicine, Szaserow 128, 04-141, Warsaw, Poland.

Novel experimental conditions of cancer cell line culture have evolved throughout the recent years, with significantly growing interest in xeno-free, serum-free and three-dimensional culture variants. The choice of proper culture media may enable to mimic tumor microenvironment and promotion of cancer stem cells proliferation. To assess whether stem-like phenotype inducing media may be applied in renal cancer stem cell research, we performed a widespread screening of 13 cell culture media dedicated for mesenchymal cells, stem cells as well as mesenchymal stem cells. Read More

View Article and Full-Text PDF
February 2019