Gene Symbol: Hif1a
Description: hypoxia inducible factor 1, alpha subunit
Alias: AA959795, HIF-1-alpha, HIF1-alpha, HIF1alpha, MOP1, bHLHe78, hypoxia-inducible factor 1-alpha, ARNT-interacting protein
Species: mouse
Products:     Hif1a

Top Publications

  1. Thomas G, Tran C, Mellinghoff I, Welsbie D, Chan E, Fueger B, et al. Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer. Nat Med. 2006;12:122-7 pubmed
    ..Growth arrest caused by CCI-779 correlates with a block in translation of mRNA encoding hypoxia-inducible factor (HIF1A), and is rescued by expression of a VHL-resistant HIF1A cDNA lacking the 5' untranslated region...
  2. Aro E, Khatri R, Gerard O Riley R, Mangiavini L, Myllyharju J, Schipani E. Hypoxia-inducible factor-1 (HIF-1) but not HIF-2 is essential for hypoxic induction of collagen prolyl 4-hydroxylases in primary newborn mouse epiphyseal growth plate chondrocytes. J Biol Chem. 2012;287:37134-44 pubmed publisher
    ..The hypoxia inducibility of the C-P4H isoenzymes is thus likely to ensure sufficient C-P4H activity for collagen synthesis occurring in chondrocytes in a hypoxic environment. ..
  3. Tannahill G, Curtis A, Adamik J, Palsson McDermott E, McGettrick A, Goel G, et al. Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature. 2013;496:238-42 pubmed publisher
    ..Lipopolysaccharide also increases succinylation of several proteins. We therefore identify succinate as a metabolite in innate immune signalling, which enhances interleukin-1β production during inflammation. ..
  4. Kim J, Evans C, Weidemann A, Takeda N, Lee Y, Stockmann C, et al. Loss of fibroblast HIF-1α accelerates tumorigenesis. Cancer Res. 2012;72:3187-95 pubmed publisher
    ..Together, our findings indicate that the fibroblast HIF-1α response is a critical component of tumor vascularization. ..
  5. Skuli N, Majmundar A, Krock B, Mesquita R, Mathew L, Quinn Z, et al. Endothelial HIF-2? regulates murine pathological angiogenesis and revascularization processes. J Clin Invest. 2012;122:1427-43 pubmed publisher
    ..These results indicate that HIF-1? and HIF-2? fulfill complementary, but largely nonoverlapping, essential functions in pathophysiological angiogenesis. ..
  6. Eckle T, Hartmann K, Bonney S, Reithel S, Mittelbronn M, Walker L, et al. Adora2b-elicited Per2 stabilization promotes a HIF-dependent metabolic switch crucial for myocardial adaptation to ischemia. Nat Med. 2012;18:774-82 pubmed publisher
  7. Lin M, Hu Y, Chen Y, Zhou K, Jin J, Zhu M, et al. Impacts of hypoxia-inducible factor-1 knockout in the retinal pigment epithelium on choroidal neovascularization. Invest Ophthalmol Vis Sci. 2012;53:6197-206 pubmed publisher
    ..The purpose of this study is to determine the role of retinal pigment epithelium (RPE)-derived HIF-1? on ocular NV...
  8. Jiang C, Kim J, Li F, Qu A, Gavrilova O, Shah Y, et al. Hypoxia-inducible factor 1? regulates a SOCS3-STAT3-adiponectin signal transduction pathway in adipocytes. J Biol Chem. 2013;288:3844-57 pubmed publisher
    ..This study provides evidence for a novel target gene and signal transduction pathway in adipocytes and indicates that inhibitors of HIF1? have potential utility for the treatment of obesity and type 2 diabetes. ..
  9. Wobben R, Hüsecken Y, Lodewick C, Gibbert K, Fandrey J, Winning S. Role of hypoxia inducible factor-1? for interferon synthesis in mouse dendritic cells. Biol Chem. 2013;394:495-505 pubmed publisher
    ..We conclude that HIF-1? plays a crucial role in DC interferon production and T cell activation, linking the innate and adaptive immune system. ..

More Information


  1. Kurihara T, Westenskow P, Bravo S, Aguilar E, Friedlander M. Targeted deletion of Vegfa in adult mice induces vision loss. J Clin Invest. 2012;122:4213-7 pubmed publisher
    ..Targeting factors upstream of VEGF, such as HIFs, may be therapeutically advantageous compared with more potent and selective VEGF antagonists, which may have more off-target inhibitory trophic effects. ..
  2. Ciofani M, Madar A, Galan C, Sellars M, Mace K, Pauli F, et al. A validated regulatory network for Th17 cell specification. Cell. 2012;151:289-303 pubmed publisher
    ..This interconnected network can be used to investigate new therapeutic approaches to manipulate Th17 functions in the setting of inflammatory disease. ..
  3. Clambey E, McNamee E, Westrich J, Glover L, Campbell E, Jedlicka P, et al. Hypoxia-inducible factor-1 alpha-dependent induction of FoxP3 drives regulatory T-cell abundance and function during inflammatory hypoxia of the mucosa. Proc Natl Acad Sci U S A. 2012;109:E2784-93 pubmed publisher
    ..Finally, Treg-intrinsic HIF-1? was required for optimal Treg function and Hif1a-deficient Tregs failed to control T-cell-mediated colitis...
  4. Rankin E, Wu C, Khatri R, Wilson T, Andersen R, Araldi E, et al. The HIF signaling pathway in osteoblasts directly modulates erythropoiesis through the production of EPO. Cell. 2012;149:63-74 pubmed publisher
    ..Furthermore, these studies demonstrate a molecular role for osteoblastic PHD/VHL/HIF signaling that can be targeted to elevate both HSCs and erythroid progenitors in the local hematopoietic microenvironment. ..
  5. Bhandari T, Olson J, Johnson R, Nizet V. HIF-1α influences myeloid cell antigen presentation and response to subcutaneous OVA vaccination. J Mol Med (Berl). 2013;91:1199-205 pubmed publisher
    ..Thus, HIF-1 participates in bridging the innate and adaptive immune responses and may merit further exploration as an adjuvant target. ..
  6. Doedens A, Phan A, Stradner M, Fujimoto J, Nguyen J, Yang E, et al. Hypoxia-inducible factors enhance the effector responses of CD8(+) T cells to persistent antigen. Nat Immunol. 2013;14:1173-82 pubmed publisher
    ..We found that HIFs and oxygen influenced the expression of pivotal transcription, effector and costimulatory-inhibitory molecules of CTLs, which was relevant to strategies that promote the clearance of viruses and tumors. ..
  7. Berger E, McClellan S, Vistisen K, Hazlett L. HIF-1α is essential for effective PMN bacterial killing, antimicrobial peptide production and apoptosis in Pseudomonas aeruginosa keratitis. PLoS Pathog. 2013;9:e1003457 pubmed publisher
  8. Woelk C, Zhang J, Walls L, Viriyakosol S, Singhania A, Kirkland T, et al. Factors regulated by interferon gamma and hypoxia-inducible factor 1A contribute to responses that protect mice from Coccidioides immitis infection. BMC Microbiol. 2012;12:218 pubmed publisher
    ..Mouse models of the disease have identified strains that are resistant (e.g. DBA/2) or susceptible (e.g. C57BL/6) to these pathogens. However, the genetic and immunological basis for this difference has not been fully characterized...
  9. Park Y, Park B, Lee S, Choi K, Moon Y, Park H. Hypoxia-inducible factor-2?-dependent hypoxic induction of Wnt10b expression in adipogenic cells. J Biol Chem. 2013;288:26311-22 pubmed publisher
    ..These results suggest that O2 concentration gradients influence the formation of Wnt ligand gradients, which are involved in the regulation of pluripotency, cell proliferation, and cell differentiation. ..
  10. Kim W, Safran M, Buckley M, Ebert B, Glickman J, Bosenberg M, et al. Failure to prolyl hydroxylate hypoxia-inducible factor alpha phenocopies VHL inactivation in vivo. EMBO J. 2006;25:4650-62 pubmed
    ..We introduced HIF1alpha and HIF2alpha variants that cannot be hydroxylated on these sites into the ubiquitously expressed ROSA26 locus ..
  11. Zhou J, Dehne N, Brüne B. Nitric oxide causes macrophage migration via the HIF-1-stimulated small GTPases Cdc42 and Rac1. Free Radic Biol Med. 2009;47:741-9 pubmed publisher
    ..Our observations strengthen the role of HIF-1 in macrophages as a target of NO in facilitating functional responses such as migration. ..
  12. Chan D, Sutphin P, Denko N, Giaccia A. Role of prolyl hydroxylation in oncogenically stabilized hypoxia-inducible factor-1alpha. J Biol Chem. 2002;277:40112-7 pubmed
    ..Thus, these results indicate distinct pathways for HIF-1alpha stabilization by different oncogenes. More importantly, these findings link oncogenesis with normoxic HIF-1alpha expression through prolyl hydroxylation. ..
  13. Zhang N, Fu Z, Linke S, Chicher J, Gorman J, Visk D, et al. The asparaginyl hydroxylase factor inhibiting HIF-1alpha is an essential regulator of metabolism. Cell Metab. 2010;11:364-78 pubmed publisher
    ..These results demonstrate that FIH acts to a significant degree through the nervous system to regulate metabolism. ..
  14. Caprara C, Thiersch M, Lange C, Joly S, Samardzija M, Grimm C. HIF1A is essential for the development of the intermediate plexus of the retinal vasculature. Invest Ophthalmol Vis Sci. 2011;52:2109-17 pubmed publisher
    b>HIF1A is one of the major transcription factors that regulate tissue response to low oxygen tension. It controls expression of a large number of genes involved in cell survival, proliferation, angiogenesis, and other cellular processes...
  15. Saini Y, Harkema J, LaPres J. HIF1alpha is essential for normal intrauterine differentiation of alveolar epithelium and surfactant production in the newborn lung of mice. J Biol Chem. 2008;283:33650-7 pubmed publisher
    ..Hypoxia-inducible factor 1alpha (HIF1alpha) is the primary transcription factor that is responsible for regulating the cellular response to changes in ..
  16. Zhang H, Bosch Marce M, Shimoda L, Tan Y, Baek J, Wesley J, et al. Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J Biol Chem. 2008;283:10892-903 pubmed publisher
  17. Cramer T, Yamanishi Y, Clausen B, Forster I, Pawlinski R, Mackman N, et al. HIF-1alpha is essential for myeloid cell-mediated inflammation. Cell. 2003;112:645-57 pubmed
    ..This role for HIF-1alpha demonstrates its direct regulation of survival and function in the inflammatory microenvironment. ..
  18. Krishnan J, Danzer C, Simka T, Ukropec J, Walter K, Kumpf S, et al. Dietary obesity-associated Hif1? activation in adipocytes restricts fatty acid oxidation and energy expenditure via suppression of the Sirt2-NAD+ system. Genes Dev. 2012;26:259-70 pubmed publisher
    ..Thus, by negatively regulating the Sirt2-Pgc1? regulatory axis, Hif1? negates adipocyte-intrinsic pathways of fatty acid catabolism, thereby creating a metabolic state supporting the development of obesity. ..
  19. Ginouves A, Ilc K, Macías N, Pouyssegur J, Berra E. PHDs overactivation during chronic hypoxia "desensitizes" HIFalpha and protects cells from necrosis. Proc Natl Acad Sci U S A. 2008;105:4745-50 pubmed publisher
    ..Hence, PHDs serve as dual enzymes, for which inactivation and later overactivation is necessary for cell survival in acute or chronic hypoxia, respectively. ..
  20. Young A, Schlisio S, Minamishima Y, Zhang Q, Li L, Grisanzio C, et al. VHL loss actuates a HIF-independent senescence programme mediated by Rb and p400. Nat Cell Biol. 2008;10:361-9 pubmed publisher
    ..Our results suggest that senescence induced by VHL inactivation is a tumour-suppressive mechanism that must be overcome to develop VHL-associated neoplasias. ..
  21. Lei L, Mason S, Liu D, Huang Y, Marks C, Hickey R, et al. Hypoxia-inducible factor-dependent degeneration, failure, and malignant transformation of the heart in the absence of the von Hippel-Lindau protein. Mol Cell Biol. 2008;28:3790-803 pubmed publisher
    ..These findings strongly suggest that chronic activation of the HIF pathway in ischemic hearts is maladaptive and contributes to cardiac degeneration and progression to heart failure. ..
  22. Fukuda R, Zhang H, Kim J, Shimoda L, Dang C, Semenza G. HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells. Cell. 2007;129:111-22 pubmed
    ..Thus, mammalian cells respond to hypoxia by altering COX subunit composition, as previously observed in yeast, but by a completely different molecular mechanism. ..
  23. Kotch L, Iyer N, Laughner E, Semenza G. Defective vascularization of HIF-1alpha-null embryos is not associated with VEGF deficiency but with mesenchymal cell death. Dev Biol. 1999;209:254-67 pubmed
    ..In Hif1a-/- knockout mice, complete deficiency of HIF-1alpha resulted in cardiac and vascular malformations and embryonic ..
  24. Cheng K, Ho K, Stokes R, Scott C, Lau S, Hawthorne W, et al. Hypoxia-inducible factor-1alpha regulates beta cell function in mouse and human islets. J Clin Invest. 2010;120:2171-83 pubmed publisher
    ..C57BL/6 mice with beta cell-specific Hif1a disruption (referred to herein as beta-Hif1a-null mice) exhibited glucose intolerance, beta cell dysfunction, and ..
  25. Lee S, Che X, Jeong J, Choi J, Lee Y, Lee Y, et al. Runx2 protein stabilizes hypoxia-inducible factor-1? through competition with von Hippel-Lindau protein (pVHL) and stimulates angiogenesis in growth plate hypertrophic chondrocytes. J Biol Chem. 2012;287:14760-71 pubmed publisher
    ..In conclusion, Runx2, HIF-1?, and VEGF may regulate vascular angiogenesis spatially and temporally in the hypertrophic zone of the growth plate during endochondral bone formation. ..
  26. Schwab L, Peacock D, Majumdar D, Ingels J, Jensen L, Smith K, et al. Hypoxia-inducible factor 1? promotes primary tumor growth and tumor-initiating cell activity in breast cancer. Breast Cancer Res. 2012;14:R6 pubmed
    ..Mammary tumor epithelial cells were created from MMTV-PyMT mice harboring conditional alleles of Hif1a, followed by transduction ex vivo with either adenovirus ?-galactosidase or adenovirus Cre to generate wild-type (..
  27. Ochiai D, Goda N, Hishiki T, Kanai M, Senoo Matsuda N, Soga T, et al. Disruption of HIF-1? in hepatocytes impairs glucose metabolism in diet-induced obesity mice. Biochem Biophys Res Commun. 2011;415:445-9 pubmed publisher
    ..These findings suggest that HIF-1 in hepatocytes plays protective roles against the progression of diabetes mellitus. ..
  28. Pfander D, Kobayashi T, Knight M, Zelzer E, Chan D, Olsen B, et al. Deletion of Vhlh in chondrocytes reduces cell proliferation and increases matrix deposition during growth plate development. Development. 2004;131:2497-508 pubmed
    ..of a ubiquitin ligase that promotes proteolysis of the transcription factor hypoxia-inducible-factor 1alpha (HIF1alpha), the key molecule in the hypoxic response...
  29. Kurihara T, Westenskow P, Krohne T, Aguilar E, Johnson R, Friedlander M. Astrocyte pVHL and HIF-? isoforms are required for embryonic-to-adult vascular transition in the eye. J Cell Biol. 2011;195:689-701 pubmed publisher
    ..The phenotype observed in Vhl mutants strongly resembles human persistent hyperplastic primary vitreous cases and may provide insights into vascular remodeling mechanisms in other systems. ..
  30. Walmsley S, Chilvers E, Thompson A, Vaughan K, Marriott H, Parker L, et al. Prolyl hydroxylase 3 (PHD3) is essential for hypoxic regulation of neutrophilic inflammation in humans and mice. J Clin Invest. 2011;121:1053-63 pubmed publisher
    ..These data support what we believe to be a novel function for PHD3 in regulating neutrophil survival in hypoxia and may enable the development of new therapeutics for inflammatory disease. ..
  31. Komatsu D, Bosch Marce M, Semenza G, Hadjiargyrou M. Enhanced bone regeneration associated with decreased apoptosis in mice with partial HIF-1alpha deficiency. J Bone Miner Res. 2007;22:366-74 pubmed
    ..Furthermore, apoptosis inhibition may be a promising target for developing new treatments to accelerate bone regeneration. ..
  32. Wenger R, Rolfs A, Spielmann P, Zimmermann D, Gassmann M. Mouse hypoxia-inducible factor-1alpha is encoded by two different mRNA isoforms: expression from a tissue-specific and a housekeeping-type promoter. Blood. 1998;91:3471-80 pubmed
    ..5% O2 for up to 72 hours) also caused a decrease in liver HIF-1alpha mRNA, whereas aldolase mRNA levels increased. These findings might be related to the relatively low Epo levels in the adult liver. ..
  33. Corzo C, Condamine T, Lu L, Cotter M, Youn J, Cheng P, et al. HIF-1? regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. J Exp Med. 2010;207:2439-53 pubmed publisher
  34. Soucek T, Cumming R, Dargusch R, Maher P, Schubert D. The regulation of glucose metabolism by HIF-1 mediates a neuroprotective response to amyloid beta peptide. Neuron. 2003;39:43-56 pubmed
    ..As a result of Abeta-induced changes in glucose metabolism, Abeta-resistant cells are more readily killed by glucose starvation and by classes of antipsychotic drugs that inhibit glucose uptake. ..
  35. Takeda N, O Dea E, Doedens A, Kim J, Weidemann A, Stockmann C, et al. Differential activation and antagonistic function of HIF-{alpha} isoforms in macrophages are essential for NO homeostasis. Genes Dev. 2010;24:491-501 pubmed publisher
  36. Weidemann A, Kerdiles Y, Knaup K, Rafie C, Boutin A, Stockmann C, et al. The glial cell response is an essential component of hypoxia-induced erythropoiesis in mice. J Clin Invest. 2009;119:3373-83 pubmed publisher
    ..Thus, we have demonstrated that the glial component of the CNS is an essential component of hypoxia-induced erythropoiesis. ..
  37. Jiang B, Agani F, Passaniti A, Semenza G. V-SRC induces expression of hypoxia-inducible factor 1 (HIF-1) and transcription of genes encoding vascular endothelial growth factor and enolase 1: involvement of HIF-1 in tumor progression. Cancer Res. 1997;57:5328-35 pubmed
    ..These studies link an oncogene to the induction of HIF-1 expression, thus providing a mechanism for hypoxic adaptation by tumor cells. ..
  38. Ng K, Lee Y, Chan Y, Lai W, Fung M, Li R, et al. Exogenous expression of HIF-1 alpha promotes cardiac differentiation of embryonic stem cells. J Mol Cell Cardiol. 2010;48:1129-37 pubmed publisher
    ..These findings suggest that keen activation of the HIF-1 pathway enhances differentiation and maturation of cardiomyocytes derived from ESCs. ..
  39. Bellot G, Garcia Medina R, Gounon P, Chiche J, Roux D, Pouyssegur J, et al. Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol Cell Biol. 2009;29:2570-81 pubmed publisher
    ..Hypoxia-induced autophagy via BNIP3 and BNIP3L is clearly a survival mechanism that promotes tumor progression. ..
  40. Kojima H, Gu H, Nomura S, Caldwell C, Kobata T, Carmeliet P, et al. Abnormal B lymphocyte development and autoimmunity in hypoxia-inducible factor 1alpha -deficient chimeric mice. Proc Natl Acad Sci U S A. 2002;99:2170-4 pubmed
    ..HIF-1alpha deficiency in Hif1alpha(-/-) --> Rag2(-/-) chimeric mice results in dramatic and cell lineage-specific defects, which include ..
  41. Torii S, Goto Y, Ishizawa T, Hoshi H, Goryo K, Yasumoto K, et al. Pro-apoptotic activity of inhibitory PAS domain protein (IPAS), a negative regulator of HIF-1, through binding to pro-survival Bcl-2 family proteins. Cell Death Differ. 2011;18:1711-25 pubmed publisher
    ..IPAS contributed to dysfunction of Bcl-x(L) by inhibiting the interaction of Bcl-x(L) with Bax. These results demonstrate that IPAS functions as a dual function protein involved in transcription repression and apoptosis. ..
  42. Chen Y, Doughman Y, Gu S, Jarrell A, Aota S, Cvekl A, et al. Cited2 is required for the proper formation of the hyaloid vasculature and for lens morphogenesis. Development. 2008;135:2939-48 pubmed publisher
    ..Deletion of Hif1a (which encodes HIF-1alpha) in Cited2(-/-) lens specifically eliminated the excessive accumulation of cellular mass ..
  43. Higgins D, Kimura K, Bernhardt W, Shrimanker N, Akai Y, Hohenstein B, et al. Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition. J Clin Invest. 2007;117:3810-20 pubmed
  44. Kim S, Choi Y, Joung S, Lee B, Jung Y, Lee J. Hypoxic stress up-regulates the expression of Toll-like receptor 4 in macrophages via hypoxia-inducible factor. Immunology. 2010;129:516-24 pubmed publisher
  45. Schipani E, Ryan H, Didrickson S, Kobayashi T, Knight M, Johnson R. Hypoxia in cartilage: HIF-1alpha is essential for chondrocyte growth arrest and survival. Genes Dev. 2001;15:2865-76 pubmed
  46. Tomita S, Sinal C, Yim S, Gonzalez F. Conditional disruption of the aryl hydrocarbon receptor nuclear translocator (Arnt) gene leads to loss of target gene induction by the aryl hydrocarbon receptor and hypoxia-inducible factor 1alpha. Mol Endocrinol. 2000;14:1674-81 pubmed
    ..These studies establish a critical role for ARNT in AHR and HIF-1alpha signal transduction in the intact mouse. ..
  47. Bridges J, Lin S, Ikegami M, Shannon J. Conditional hypoxia inducible factor-1? induction in embryonic pulmonary epithelium impairs maturation and augments lymphangiogenesis. Dev Biol. 2012;362:24-41 pubmed publisher
    ..To further assess the role of the HIF1a isoform in lung epithelial cell differentiation and homeostasis, we created transgenic mice that express a ..
  48. Shah Y, Ito S, Morimura K, Chen C, Yim S, Haase V, et al. Hypoxia-inducible factor augments experimental colitis through an MIF-dependent inflammatory signaling cascade. Gastroenterology. 2008;134:2036-48, 2048.e1-3 pubmed publisher
  49. Kurihara T, Kubota Y, Ozawa Y, Takubo K, Noda K, Simon M, et al. von Hippel-Lindau protein regulates transition from the fetal to the adult circulatory system in retina. Development. 2010;137:1563-71 pubmed publisher
    ..Our results suggest that not only macrophages but also tissue oxygen-sensing mechanisms regulate the transition from the fetal to the adult circulatory system in the retina. ..
  50. Tomita S, Ueno M, Sakamoto M, Kitahama Y, Ueki M, Maekawa N, et al. Defective brain development in mice lacking the Hif-1alpha gene in neural cells. Mol Cell Biol. 2003;23:6739-49 pubmed
  51. Flamme I, Frohlich T, von Reutern M, Kappel A, Damert A, Risau W. HRF, a putative basic helix-loop-helix-PAS-domain transcription factor is closely related to hypoxia-inducible factor-1 alpha and developmentally expressed in blood vessels. Mech Dev. 1997;63:51-60 pubmed
  52. Goda N, Ryan H, Khadivi B, McNulty W, Rickert R, Johnson R. Hypoxia-inducible factor 1alpha is essential for cell cycle arrest during hypoxia. Mol Cell Biol. 2003;23:359-69 pubmed
    ..These data demonstrate that the transcription factor HIF-1 is a major regulator of cell cycle arrest in primary cells during hypoxia. ..
  53. Xie L, Johnson R, Freeman R. Inhibition of NGF deprivation-induced death by low oxygen involves suppression of BIMEL and activation of HIF-1. J Cell Biol. 2005;168:911-20 pubmed
    ..These data suggest a new model for how O(2) tension can influence apoptotic events that underlie trophic factor deprivation-induced cell death. ..
  54. Ramanathan M, Luo W, Csóka B, Hasko G, Lukashev D, Sitkovsky M, et al. Differential regulation of HIF-1alpha isoforms in murine macrophages by TLR4 and adenosine A(2A) receptor agonists. J Leukoc Biol. 2009;86:681-9 pubmed publisher
    ..LPS-induced expression of A(2A)Rs and HIF-1alpha and A(2A)R-dependent HIF-1alpha mRNA and protein stabilization provide mechanisms for the synergistic effects of LPS and A(2A)R agonists on macrophage VEGF expression. ..
  55. Rempe D, Vangeison G, Hamilton J, Li Y, Jepson M, Federoff H. Synapsin I Cre transgene expression in male mice produces germline recombination in progeny. Genesis. 2006;44:44-9 pubmed
    ..This observation should alert investigators to a potential confound using these mice and enables male germ cell "deletor" strategies. ..
  56. Ikejiri A, Nagai S, Goda N, Kurebayashi Y, Osada Oka M, Takubo K, et al. Dynamic regulation of Th17 differentiation by oxygen concentrations. Int Immunol. 2012;24:137-46 pubmed publisher
    ..Thus, a positive feedback loop between HIF-1? and mTORC1 induced by hypoxia followed by reoxygenation accelerates T(h)17-cell differentiation. ..
  57. Wang Y, Wan C, Deng L, Liu X, Cao X, Gilbert S, et al. The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. J Clin Invest. 2007;117:1616-26 pubmed
    ..By contrast, mice lacking Hif1a in osteoblasts had the reverse skeletal phenotype of that of the Vhl mutants: long bones were significantly ..
  58. Eckle T, Kohler D, Lehmann R, El Kasmi K, Eltzschig H. Hypoxia-inducible factor-1 is central to cardioprotection: a new paradigm for ischemic preconditioning. Circulation. 2008;118:166-75 pubmed publisher
    ..Taken together, these studies provide evidence for a critical role of HIF-1 in ischemic preconditioning via enhancing purinergic signaling pathways. ..
  59. Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, et al. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science. 2001;292:464-8 pubmed
    ..Because proline hydroxylation requires molecular oxygen and Fe(2+), this protein modification may play a key role in mammalian oxygen sensing. ..
  60. Huss W, Hanrahan C, Barrios R, Simons J, Greenberg N. Angiogenesis and prostate cancer: identification of a molecular progression switch. Cancer Res. 2001;61:2736-43 pubmed
  61. Ryan H, Poloni M, McNulty W, Elson D, Gassmann M, Arbeit J, et al. Hypoxia-inducible factor-1alpha is a positive factor in solid tumor growth. Cancer Res. 2000;60:4010-5 pubmed
    ..The evidence from these experiments indicates that hypoxic response via HIF-1alpha is an important positive factor in solid tumor growth and that HIF-1alpha affects tumor expansion in ways unrelated to its regulation of VEGF expression. ..
  62. Botusan I, Sunkari V, Savu O, Catrina A, Grunler J, Lindberg S, et al. Stabilization of HIF-1alpha is critical to improve wound healing in diabetic mice. Proc Natl Acad Sci U S A. 2008;105:19426-31 pubmed publisher
    ..In conclusion, we demonstrate that impaired regulation of HIF-1alpha is essential for the development of diabetic wounds, and we provide evidence that stabilization of HIF-1alpha is critical to reverse the pathological process. ..
  63. Zhang X, Lam K, Ye H, Chung S, Zhou M, Wang Y, et al. Adipose tissue-specific inhibition of hypoxia-inducible factor 1{alpha} induces obesity and glucose intolerance by impeding energy expenditure in mice. J Biol Chem. 2010;285:32869-77 pubmed publisher
    ..These findings support an indispensable role of HIF1? in maintaining the thermogenic functions of BAT, possibly through promoting angiogenesis and mitochondrial biogenesis in this tissue. ..
  64. Zhong L, D Urso A, Toiber D, Sebastian C, Henry R, Vadysirisack D, et al. The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha. Cell. 2010;140:280-93 pubmed publisher
    ..Specifically, SIRT6 appears to function as a corepressor of the transcription factor Hif1alpha, a critical regulator of nutrient stress responses...
  65. Iyer N, Kotch L, Agani F, Leung S, Laughner E, Wenger R, et al. Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha. Genes Dev. 1998;12:149-62 pubmed
    ..We now report that in Hif1a-/- embryonic stem cells that did not express the O2-regulated HIF-1alpha subunit, levels of mRNAs encoding glucose ..
  66. Cantley J, Selman C, Shukla D, Abramov A, Forstreuter F, Esteban M, et al. Deletion of the von Hippel-Lindau gene in pancreatic beta cells impairs glucose homeostasis in mice. J Clin Invest. 2009;119:125-35 pubmed publisher
    ..The abnormal glucose homeostasis was dependent on upregulation of Hif-1alpha expression, and deletion of Hif1a in Vhl-deficient beta cells restored GSIS...
  67. Tian H, McKnight S, Russell D. Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. Genes Dev. 1997;11:72-82 pubmed
    ..These observations raise the possibility that EPAS1 may represent an important regulator of vascularization, perhaps involving the regulation of endothelial cell gene expression in response to hypoxia. ..
  68. Jeon S, Chae B, Kim H, Seo G, Seo D, Chun G, et al. Mechanisms underlying TGF-beta1-induced expression of VEGF and Flk-1 in mouse macrophages and their implications for angiogenesis. J Leukoc Biol. 2007;81:557-66 pubmed
    ..The results from the present study indicate that TGF-beta1 can activate mouse macrophages to express angiogenic mediators such as VEGF, MMP-9, and Flk-1. ..
  69. Carmeliet P, Dor Y, Herbert J, Fukumura D, Brusselmans K, Dewerchin M, et al. Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature. 1998;394:485-90 pubmed
    ..As hypoxic stress contributes to many (patho)biological disorders, this new role for HIF-1alpha in hypoxic control of cell growth and death may be of general pathophysiological importance. ..
  70. Fan X, Heijnen C, van der Kooij M, Groenendaal F, van Bel F. The role and regulation of hypoxia-inducible factor-1alpha expression in brain development and neonatal hypoxic-ischemic brain injury. Brain Res Rev. 2009;62:99-108 pubmed publisher
    ..These events are cell type specific and related to the severity of hypoxia. Unravelling of the complex functions of HIF-1alpha may be important when designing neuroprotective therapies for hypoxic-ischemic brain injury. ..
  71. Garcia C, Shui Y, Kamath M, DeVillar J, Johnson R, Gerber H, et al. The function of VEGF-A in lens development: formation of the hyaloid capillary network and protection against transient nuclear cataracts. Exp Eye Res. 2009;88:270-6 pubmed publisher
    ..Lenses lacking Hif1a were of apparently normal size, had markedly reduced levels of mRNA for VEGF-A and glyceraldehyde-3-phosphate ..
  72. Shui Y, Arbeit J, Johnson R, Beebe D. HIF-1: an age-dependent regulator of lens cell proliferation. Invest Ophthalmol Vis Sci. 2008;49:4961-70 pubmed publisher
    ..Transgenic mice expressing Cre recombinase in the lens were bred to mice containing floxed Hif1a alleles...
  73. Liao D, Corle C, Seagroves T, Johnson R. Hypoxia-inducible factor-1alpha is a key regulator of metastasis in a transgenic model of cancer initiation and progression. Cancer Res. 2007;67:563-72 pubmed
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    ..Furthermore, we provide evidence that hepatocyte-derived Hif-2 is involved in the regulation of iron metabolism genes, supporting a role for HIF-2 in the coordination of EPO synthesis with iron homeostasis. ..
  75. Ema M, Taya S, Yokotani N, Sogawa K, Matsuda Y, Fujii Kuriyama Y. A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1alpha regulates the VEGF expression and is potentially involved in lung and vascular development. Proc Natl Acad Sci U S A. 1997;94:4273-8 pubmed
    ..and its predicted amino acid sequence exhibits significant similarity to the hypoxia-inducible factor 1alpha (HIF1alpha) and Drosophila trachealess (dTrh) gene product...
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    ..These data demonstrate the essential role of HIF-1alpha in controlling both embryonic and tumorigenic responses to variations in microenvironmental oxygenation. ..
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    ..These results provide genetic evidence that p38 mitogen-activated protein kinase signaling is essential for HIF-1 activation. ..
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    ..Overall, the continuous bioluminescence readout of HIF-1alpha/FLuc stabilization in vitro and in vivo will facilitate the development and validation of therapeutics that affect the stability and accumulation of HIF-1alpha. ..
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    ..In addition, our data suggest that HIF-1alpha plays a role in the survival and self-renewal potential of CSCs and identify genes that might further elucidate the role of HIF-1alpha in tumor migration, invasion and stem cell biology. ..
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    ..Together, these data suggest that HIF and O(2) tension influence placental invasion and tumor migration by increasing cell surface expression of alphavbeta3 integrin. ..
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    ..Inhibition of HIF-1alpha activity may thus represent a novel therapeutic target for LPS-induced sepsis. ..
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    b>Hypoxia inducible factor 1 alpha (HIF-1 alpha) is a basic helix-loop-helix-PAS (bHLH-PAS) transcription factor that mediates certain cellular responses to low oxygen tension, iron chelators, Co2+, Ni2+, Mg2+, and low intracellular glucose ..