Epas1

Summary

Gene Symbol: Epas1
Description: endothelial PAS domain protein 1
Alias: HIF-2 alpha, HIF2 alpha, HLF, Hif2a, endothelial PAS domain-containing protein 1, EPAS-1, HIF-2-alpha, HIF2-alpha, hypoxia inducible factor 2, alpha subunit, hypoxia inducible factor 2a, hypoxia-inducible factor 2-alpha
Species: rat
Products:     Epas1

Top Publications

  1. Ohtomo S, Nangaku M, Izuhara Y, Takizawa S, Strihou C, Miyata T. Cobalt ameliorates renal injury in an obese, hypertensive type 2 diabetes rat model. Nephrol Dial Transplant. 2008;23:1166-72 pubmed
    ..Cobalt achieved renal protection independently of metabolic status and blood pressure. Its effect was attributed to the upregulation of HIF and HIF-regulated genes and to a mitigated advanced glycation and oxidative stress. ..
  2. 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
    Here we describe the cloning and characterization of a PAS domain transcription factor termed endothelial PAS-1 (EPAS1)...
  3. Bernhardt W, Wiesener M, Weidemann A, Schmitt R, Weichert W, Lechler P, et al. Involvement of hypoxia-inducible transcription factors in polycystic kidney disease. Am J Pathol. 2007;170:830-42 pubmed
    ..In conclusion, HIF accumulation in human and rat PKD seems to be responsible for increased EPO production and pericystic hypervascularity and may have an impact on progression of PKD...
  4. Tian H, Hammer R, Matsumoto A, Russell D, McKnight S. The hypoxia-responsive transcription factor EPAS1 is essential for catecholamine homeostasis and protection against heart failure during embryonic development. Genes Dev. 1998;12:3320-4 pubmed
    Mice lacking the hypoxia-inducible transcription factor EPAS1 die at mid-gestation. Despite normal morphological development of the circulatory system, EPAS1-deficient mice display pronounced bradycardia...
  5. Bracken C, Fedele A, Linke S, Balrak W, Lisy K, Whitelaw M, et al. Cell-specific regulation of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha stabilization and transactivation in a graded oxygen environment. J Biol Chem. 2006;281:22575-85 pubmed
    ..Interestingly, the initial stabilization of HIF-alpha prior to transactivation up-regulation predicted from in vitro derived hydroxylation data is only true for a subset of cells. ..
  6. Hara S, Hamada J, Kobayashi C, Kondo Y, Imura N. Expression and characterization of hypoxia-inducible factor (HIF)-3alpha in human kidney: suppression of HIF-mediated gene expression by HIF-3alpha. Biochem Biophys Res Commun. 2001;287:808-13 pubmed
    ..Furthermore, we performed reporter gene analysis and showed that HIF-3alpha suppresses hypoxia-inducible HIF-mediated gene expression. HIF-3alpha might be a negative regulator of hypoxia-inducible gene expression in the human kidney. ..
  7. Yang S, Kim J, Ryu J, Oh H, Chun C, Kim B, et al. Hypoxia-inducible factor-2alpha is a catabolic regulator of osteoarthritic cartilage destruction. Nat Med. 2010;16:687-93 pubmed publisher
    ..Here, we show that hypoxia-inducible factor-2alpha (HIF-2alpha, encoded by EPAS1) is a catabolic transcription factor in the osteoarthritic process...
  8. Bernhardt W, Campean V, Kany S, Jurgensen J, Weidemann A, Warnecke C, et al. Preconditional activation of hypoxia-inducible factors ameliorates ischemic acute renal failure. J Am Soc Nephrol. 2006;17:1970-8 pubmed
    ..Inhibiting the activity of HIF hydroxylases therefore seems to have considerable clinical perspectives. ..
  9. Compernolle V, Brusselmans K, Acker T, Hoet P, Tjwa M, Beck H, et al. Loss of HIF-2alpha and inhibition of VEGF impair fetal lung maturation, whereas treatment with VEGF prevents fatal respiratory distress in premature mice. Nat Med. 2002;8:702-10 pubmed
    ..The pneumotrophic effect of VEGF may have therapeutic potential for lung maturation in preterm infants. ..

More Information

Publications82

  1. 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
    ..The HIF1alpha-like factor (HLF) encoded by the isolated cDNA bound the hypoxia-response element (HRE) found in enhancers of genes for ..
  2. Choi S, Shin I, Je K, Min E, Kim E, Kim H, et al. Hypoxia antagonizes glucose deprivation on interleukin 6 expression in an Akt dependent, but HIF-1/2? independent manner. PLoS ONE. 2013;8:e58662 pubmed publisher
    ..However, inhibition of HIF-1/2? did not reverse the effects of hypoxia on IL-6 gene expression. In addition, phosphorylation of p38, but not JNK, was responsible for the effects of glucose deprivation on IL-6 gene expression. ..
  3. Sacramento J, Ribeiro M, Rodrigues T, Guarino M, Diogo L, Seiça R, et al. Insulin resistance is associated with tissue-specific regulation of HIF-1? and HIF-2? during mild chronic intermittent hypoxia. Respir Physiol Neurobiol. 2016;228:30-8 pubmed publisher
    ..We concluded that the effect of CIH on insulin sensitivity and signaling is time-dependent and is associated with changes in HIF signaling in insulin-sensitive tissues...
  4. Elvert G, Kappel A, Heidenreich R, Englmeier U, Lanz S, Acker T, et al. Cooperative interaction of hypoxia-inducible factor-2alpha (HIF-2alpha ) and Ets-1 in the transcriptional activation of vascular endothelial growth factor receptor-2 (Flk-1). J Biol Chem. 2003;278:7520-30 pubmed
  5. Rosenberger C, Griethe W, Gruber G, Wiesener M, Frei U, Bachmann S, et al. Cellular responses to hypoxia after renal segmental infarction. Kidney Int. 2003;64:874-86 pubmed
    ..Our findings illustrate a marked potential of renal tissue to respond to regional ischemia and initiate adaptive reactions, including angiogenesis. ..
  6. Xu J, Yang Y, Tang F, Ga Q, Tana W, Ge R. EPAS1 Gene Polymorphisms Are Associated With High Altitude Polycythemia in Tibetans at the Qinghai-Tibetan Plateau. Wilderness Environ Med. 2015;26:288-94 pubmed publisher
    To test the hypothesis that the polymorphisms in the EPAS1 gene are associated with the susceptibility to high altitude polycythemia (HAPC) in Tibetans at the Qinghai-Tibetan Plateau...
  7. Cowden Dahl K, Fryer B, Mack F, Compernolle V, Maltepe E, Adelman D, et al. Hypoxia-inducible factors 1alpha and 2alpha regulate trophoblast differentiation. Mol Cell Biol. 2005;25:10479-91 pubmed
    ..This novel genetic approach provides new insights into the role of O2 tension in the development of life-threatening pregnancy-related diseases such as preeclampsia. ..
  8. Scortegagna M, Ding K, Zhang Q, Oktay Y, Bennett M, Bennett M, et al. HIF-2alpha regulates murine hematopoietic development in an erythropoietin-dependent manner. Blood. 2005;105:3133-40 pubmed
    ..We previously reported that mice lacking wild-type HIF-2alpha, encoded by the EPAS1 gene, exhibit pancytopenia. In this study, we have characterized the etiology of this hematopoietic phenotype...
  9. Okamoto N, Tanaka A, Jung K, Karasawa K, Orito K, Matsuda A, et al. Silencing of int6 gene restores function of the ischaemic hindlimb in a rat model of peripheral arterial disease. Cardiovasc Res. 2011;92:209-17 pubmed publisher
    ..In this study, we examined the clinical efficacy of silencing the int6 gene, which encodes a protein that stabilizes hypoxia-inducible factor (HIF)-2?, on angiogenesis in PAD...
  10. Rao K, Sethi K, Ischia J, Gibson L, Galea L, Xiao L, et al. Protective effect of zinc preconditioning against renal ischemia reperfusion injury is dose dependent. PLoS ONE. 2017;12:e0180028 pubmed publisher
    ..ZnCl2 preconditioning protects against renal IRI in a dose-dependent manner. Further studies are warranted to determine the possible mechanisms involved, and to assess the benefit of ZnCl2 preconditioning for clinical applications. ..
  11. Li Q, Dai A. Differential expression of three hypoxia-inducible factor-alpha subunits in pulmonary arteries of rat with hypoxia-induced hypertension. Acta Biochim Biophys Sin (Shanghai). 2005;37:665-72 pubmed
    ..Our study found that HIF-1alpha, HIF-2alpha and HIF-3alpha may not only confer different target genes, but also play key pathogenetic roles in hypoxic-induced pulmonary hypertension. ..
  12. Gale D, Harten S, Reid C, Tuddenham E, Maxwell P. Autosomal dominant erythrocytosis and pulmonary arterial hypertension associated with an activating HIF2 alpha mutation. Blood. 2008;112:919-21 pubmed publisher
  13. Lim C, Qiao X, Reslan O, Xia Y, Raffetto J, Paleolog E, et al. Prolonged mechanical stretch is associated with upregulation of hypoxia-inducible factors and reduced contraction in rat inferior vena cava. J Vasc Surg. 2011;53:764-73 pubmed publisher
  14. Lam S, Liong E, Tipoe G, Fung M. Expression of HIF-2alpha and HIF-3alpha in the rat carotid body in chronic hypoxia. Adv Exp Med Biol. 2006;580:29-36; discussion 351-9 pubmed
  15. Xie L, Collins J. Transcriptional regulation of the Menkes copper ATPase (Atp7a) gene by hypoxia-inducible factor (HIF2{alpha}) in intestinal epithelial cells. Am J Physiol Cell Physiol. 2011;300:C1298-305 pubmed publisher
    ..In conclusion, the Atp7a gene is upregulated by direct interaction with HIF2α, demonstrating coordinate regulation with genes related to intestinal iron homeostasis. ..
  16. Nakajima M, Shi D, Dai J, Tsezou A, Zheng M, Norman P, et al. A large-scale replication study for the association of rs17039192 in HIF-2? with knee osteoarthritis. J Orthop Res. 2012;30:1244-8 pubmed publisher
    ..81-1.03). Our large-scale meta-analysis showed that the association of rs17039192 in HIF-2? with knee OA is negative. The significance of HIF-2? in human OA (idiopathic OA as a common disease) should be further evaluated carefully. ..
  17. Duan L, Zhang Benoit Y, Fong G. Endothelium-intrinsic requirement for Hif-2alpha during vascular development. Circulation. 2005;111:2227-32 pubmed
    ..These data demonstrate an intrinsic requirement for Hif-2alpha by endothelial cells and imply that hypoxia may control endothelial functions directly via Hif-2alpha-regulated Tie-2 expression. ..
  18. Rosenberger C, Rosen S, Shina A, Frei U, Eckardt K, Flippin L, et al. Activation of hypoxia-inducible factors ameliorates hypoxic distal tubular injury in the isolated perfused rat kidney. Nephrol Dial Transplant. 2008;23:3472-8 pubmed publisher
    ..mTAL conservation may be related to the stabilization of cellular HIF, as well as to preserved endothelial function and microcirculation. ..
  19. Oktay Y, Dioum E, Matsuzaki S, Ding K, Yan L, Haller R, et al. Hypoxia-inducible factor 2alpha regulates expression of the mitochondrial aconitase chaperone protein frataxin. J Biol Chem. 2007;282:11750-6 pubmed
    Mice lacking Epas1, encoding the transcription factor Hypoxia-inducible Factor 2alpha (HIF-2alpha), exhibit an apparent mitochondrial disease state...
  20. Milkiewicz M, Doyle J, Fudalewski T, Ispanovic E, Aghasi M, Haas T. HIF-1alpha and HIF-2alpha play a central role in stretch-induced but not shear-stress-induced angiogenesis in rat skeletal muscle. J Physiol. 2007;583:753-66 pubmed
    ..Together, these results illustrate that activation of HIF-1alpha and HIF-2alpha contributes significantly to stretch- but not to shear-stress-induced capillary growth. ..
  21. Tanaka T, Akiyama H, Kanai H, Sato M, Takeda S, Sekiguchi K, et al. Endothelial PAS domain protein 1 (EPAS1) induces adrenomedullin gene expression in cardiac myocytes: role of EPAS1 in an inflammatory response in cardiac myocytes. J Mol Cell Cardiol. 2002;34:739-48 pubmed
    Endothelial PAS domain protein 1 (EPAS1) has been identified as a member of the basic helix-loop-helix (bHLH)-PAS protein family, and plays a critical role in the regulation of hypoxia inducible genes...
  22. Li Q, Dai A. [Differential expression of the three hypoxia-inducible factor alpha subunits in pulmonary artery of rats with hypoxia-induced pulmonary hypertension]. Zhonghua Jie He He Hu Xi Za Zhi. 2006;29:113-7 pubmed
    ..The differential expression of the three HIF-alpha subunits may play a role in the development of hypoxia-induced pulmonary hypertension. ..
  23. Kietzmann T, Cornesse Y, Brechtel K, Modaressi S, Jungermann K. Perivenous expression of the mRNA of the three hypoxia-inducible factor alpha-subunits, HIF1alpha, HIF2alpha and HIF3alpha, in rat liver. Biochem J. 2001;354:531-7 pubmed
    ..The mRNAs of the rat HIF alpha-subunits were expressed predominantly in the perivenous zone of rat liver tissue; the nuclear HIFalpha proteins, however, did not appear to be zonated. ..
  24. Ryu J, Shin Y, Huh Y, Yang S, Chun C, Chun J. Hypoxia-inducible factor-2? regulates Fas-mediated chondrocyte apoptosis during osteoarthritic cartilage destruction. Cell Death Differ. 2012;19:440-50 pubmed publisher
    ..Recently, we demonstrated that hypoxia-inducible factor (HIF)-2?, encoded by Epas1, causes OA cartilage destruction by regulating the expression of various matrix-degrading enzymes...
  25. Bautista L, Castro M, Lopez Barneo J, Castellano A. Hypoxia inducible factor-2alpha stabilization and maxi-K+ channel beta1-subunit gene repression by hypoxia in cardiac myocytes: role in preconditioning. Circ Res. 2009;104:1364-72 pubmed publisher
    ..Our work provides new perspectives for research on cardiac preconditioning. ..
  26. Skubutyte R, Markova D, Freeman T, Anderson D, Dion A, Williams C, et al. Hypoxia-inducible factor regulation of ANK expression in nucleus pulposus cells: possible implications in controlling dystrophic mineralization in the intervertebral disc. Arthritis Rheum. 2010;62:2707-15 pubmed publisher
    ..Both HIF-1 and HIF-2 serve as negative regulators of ANK expression in the disc. We propose that baseline expression of ANK in the disc serves to prevent mineral formation under physiologic conditions. ..
  27. Vadivel A, Alphonse R, Etches N, van Haaften T, Collins J, O Reilly M, et al. Hypoxia-inducible factors promote alveolar development and regeneration. Am J Respir Cell Mol Biol. 2014;50:96-105 pubmed publisher
    ..HIFs promote normal alveolar development and may be useful targets for alveolar regeneration. ..
  28. Yu L, Hales C. Long-term exposure to hypoxia inhibits tumor progression of lung cancer in rats and mice. BMC Cancer. 2011;11:331 pubmed publisher
    ..The results from this study provide new insights into the role of hypoxia in tumor progression and therapeutic strategies for cancer treatment. ..
  29. Brown S, Nurse C. Induction of HIF-2alpha is dependent on mitochondrial O2 consumption in an O2-sensitive adrenomedullary chromaffin cell line. Am J Physiol Cell Physiol. 2008;294:C1305-12 pubmed publisher
    ..These data suggest that in this O2-sensitive cell line, mitochondrial O2 consumption, rather than changes in ROS, regulates HIF-2alpha during hypoxia. ..
  30. Chen Y, Dai A, Hu R, Jiang Y. Differential and reciprocal regulation between hypoxia-inducible factor-alpha subunits and their prolyl hydroxylases in pulmonary arteries of rat with hypoxia-induced hypertension. Acta Biochim Biophys Sin (Shanghai). 2006;38:423-34 pubmed
    ..In the present study, HIF-alpha subunits and PHDs showed differential and reciprocal regulation, and this might play a key pathogenesis role in hypoxia-induced pulmonary hypertension. ..
  31. Hui A, Bauer A, Striet J, Schnell P, Czyzyk Krzeska M. Calcium signaling stimulates translation of HIF-alpha during hypoxia. FASEB J. 2006;20:466-75 pubmed
  32. Scortegagna M, Morris M, Oktay Y, Bennett M, Garcia J. The HIF family member EPAS1/HIF-2alpha is required for normal hematopoiesis in mice. Blood. 2003;102:1634-40 pubmed
    ..After generating adult mice that globally lack endothelial PAS domain protein 1 (EPAS1, also known as HIF-2alpha/HRF/HLF/MOP3), the second member of the HIF family, characterization of the ..
  33. An H, Shin H, Jo S, Kim Y, Lee J, Paik S, et al. The survival effect of mitochondrial Higd-1a is associated with suppression of cytochrome C release and prevention of caspase activation. Biochim Biophys Acta. 2011;1813:2088-98 pubmed publisher
    ..Together these observations indicate that Higd-1a is induced by hypoxia in a HIF-dependent manner and its anti-apoptotic effect results from inhibiting cytochrome C release and reducing caspase activities. ..
  34. 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. ..
  35. Giatromanolaki A, Sivridis E, Maltezos E, Athanassou N, Papazoglou D, Gatter K, et al. Upregulated hypoxia inducible factor-1alpha and -2alpha pathway in rheumatoid arthritis and osteoarthritis. Arthritis Res Ther. 2003;5:R193-201 pubmed
    ..The activation of the HIF-alpha pathway occurs in both RA and OA, although for unrelated reasons. ..
  36. Loboda A, Jozkowicz A, Dulak J. HIF-1 and HIF-2 transcription factors--similar but not identical. Mol Cells. 2010;29:435-42 pubmed publisher
    ..Finally, recent data showing link between HIFs and specific microRNA have been presented. ..
  37. Keith B, Johnson R, Simon M. HIF1? and HIF2?: sibling rivalry in hypoxic tumour growth and progression. Nat Rev Cancer. 2011;12:9-22 pubmed publisher
    ..As HIF inhibitors are currently undergoing clinical evaluation as cancer therapeutics, a more thorough understanding of the unique roles performed by HIF1? and HIF2? in human neoplasia is warranted. ..
  38. Mastrogiannaki M, Matak P, Delga S, Deschemin J, Vaulont S, Peyssonnaux C. Deletion of HIF-2? in the enterocytes decreases the severity of tissue iron loading in hepcidin knockout mice. Blood. 2012;119:587-90 pubmed publisher
    ..This study highlights a role of HIF-2 in the dysregulation of iron absorption and chronic iron accumulation, as observed in patients with hemochromatosis. ..
  39. Wright W, McElhatten R, Messina J, Harris N. Hypoxia and the expression of HIF-1alpha and HIF-2alpha in the retina of streptozotocin-injected mice and rats. Exp Eye Res. 2010;90:405-12 pubmed publisher
    ..In summary, despite early decreases in flow in rats and mice, retinal HIF-1alpha and HIF-2alpha were not found to be increased, and the extent of hypoxia may even decrease after 12 weeks of hyperglycemia in rats. ..
  40. Hogenesch J, Gu Y, Jain S, Bradfield C. The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors. Proc Natl Acad Sci U S A. 1998;95:5474-9 pubmed
    ..Finally, we found that MOP3 mRNA expression overlaps in a number of tissues with each of its four potential partner molecules in vivo. ..
  41. Ekman M, Uvelius B, Albinsson S, Swärd K. HIF-mediated metabolic switching in bladder outlet obstruction mitigates the relaxing effect of mitochondrial inhibition. Lab Invest. 2014;94:557-68 pubmed publisher
    ..This metabolic adaptation encompasses increased expression of glucose transporters and glycolytic enzymes combined with mitochondrial remodeling. Together, these changes uphold contractility when mitochondrial respiration is limited. ..
  42. Rosenberger C, Solovan C, Rosenberger A, Jinping L, Treudler R, Frei U, et al. Upregulation of hypoxia-inducible factors in normal and psoriatic skin. J Invest Dermatol. 2007;127:2445-52 pubmed
    ..Furthermore, such a cycle may exist in psoriasis in dermal capillaries and contribute to disease progression. ..
  43. Proper S, Saini Y, Greenwood K, Bramble L, Downing N, Harkema J, et al. Loss of hypoxia-inducible factor 2 alpha in the lung alveolar epithelium of mice leads to enhanced eosinophilic inflammation in cobalt-induced lung injury. Toxicol Sci. 2014;137:447-57 pubmed publisher
  44. Scortegagna M, Ding K, Oktay Y, Gaur A, Thurmond F, Yan L, et al. Multiple organ pathology, metabolic abnormalities and impaired homeostasis of reactive oxygen species in Epas1-/- mice. Nat Genet. 2003;35:331-40 pubmed
    ..We report that mice lacking the HIF family member HIF-2alpha (encoded by Epas1) have a syndrome of multiple-organ pathology, biochemical abnormalities and altered gene expression patterns...
  45. Kung A, Zabludoff S, France D, Freedman S, Tanner E, Vieira A, et al. Small molecule blockade of transcriptional coactivation of the hypoxia-inducible factor pathway. Cancer Cell. 2004;6:33-43 pubmed
  46. Schietke R, Hackenbeck T, Tran M, Günther R, Klanke B, Warnecke C, et al. Renal tubular HIF-2? expression requires VHL inactivation and causes fibrosis and cysts. PLoS ONE. 2012;7:e31034 pubmed publisher
    ..However, HIF-2? overexpression alone is insufficient to induce tumors. Thus, our data bear implications for renal tumorigenesis, epithelial differentiation and renal repair mechanisms. ..
  47. Santana Rodríguez N, García Herrera R, Clavo B, Llontop P, Ponce González M, Villar J, et al. Searching for novel molecular targets of chronic rejection in an orthotopic experimental lung transplantation model. J Heart Lung Transplant. 2012;31:213-21 pubmed publisher
    ..We found significantly increased mRNA expression of the Cldn5, Epas1, Tgfb1, Vegf, Selp1, Hsp27 and Igf1 genes...
  48. Saito T, Fukai A, Mabuchi A, Ikeda T, Yano F, Ohba S, et al. Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development. Nat Med. 2010;16:678-86 pubmed publisher
    ..A COL10A1 promoter assay identified hypoxia-inducible factor-2alpha (HIF-2alpha, encoded by EPAS1) as the most potent transactivator of COL10A1...
  49. Gruber M, Hu C, Johnson R, Brown E, Keith B, Simon M. Acute postnatal ablation of Hif-2alpha results in anemia. Proc Natl Acad Sci U S A. 2007;104:2301-6 pubmed
  50. Schnell P, Ignacak M, Bauer A, Striet J, Paulding W, Czyzyk Krzeska M. Regulation of tyrosine hydroxylase promoter activity by the von Hippel-Lindau tumor suppressor protein and hypoxia-inducible transcription factors. J Neurochem. 2003;85:483-91 pubmed
    ..These results indicate that HIFs may play an important role in regulation of TH gene expression in oxygen-sensitive cells and also in the development of hypercatecholaminemia in pheochromocytoma tumors. ..
  51. Yeh K, Yeh M, Polk P, Glass J. Hypoxia-inducible factor-2? and iron absorptive gene expression in Belgrade rat intestine. Am J Physiol Gastrointest Liver Physiol. 2011;301:G82-90 pubmed publisher
  52. Jurgensen J, Rosenberger C, Wiesener M, Warnecke C, Hörstrup J, Grafe M, et al. Persistent induction of HIF-1alpha and -2alpha in cardiomyocytes and stromal cells of ischemic myocardium. FASEB J. 2004;18:1415-7 pubmed
    ..Cardiomyocytes and cardiac stromal cells exhibit a marked potential for a prolonged transcriptional response to ischemia mediated by HIF. The induction of HIF-1alpha and -2alpha appears to be complementary rather than solely redundant. ..
  53. Ralph G, Parham S, Lee S, Beard G, Craigon M, Ward N, et al. Identification of potential stroke targets by lentiviral vector mediated overexpression of HIF-1 alpha and HIF-2 alpha in a primary neuronal model of hypoxia. J Cereb Blood Flow Metab. 2004;24:245-58 pubmed
    ..Further investigation of the genes identified in this study may provide increased understanding of the neuronal response to hypoxia and may uncover novel therapeutic targets for the treatment of cerebral ischemia. ..
  54. Liu M, Poellinger L, Walker C. Up-regulation of hypoxia-inducible factor 2alpha in renal cell carcinoma associated with loss of Tsc-2 tumor suppressor gene. Cancer Res. 2003;63:2675-80 pubmed
  55. Jimenez K, Khare V, Evstatiev R, Kulnigg Dabsch S, Jambrich M, Strobl H, et al. Increased expression of HIF2α during iron deficiency-associated megakaryocytic differentiation. J Thromb Haemost. 2015;13:1113-27 pubmed publisher
    ..In conclusion, the data demonstrate that iron deficiency augments megakaryocytic differentiation and proplatelet formation and a potential role of HIF2α in megakaryopoiesis. ..
  56. Peng J, Zhang L, Drysdale L, Fong G. The transcription factor EPAS-1/hypoxia-inducible factor 2alpha plays an important role in vascular remodeling. Proc Natl Acad Sci U S A. 2000;97:8386-91 pubmed
    ..Our results suggest that EPAS-1 plays an important role at postvasculogenesis stages and is required for the remodeling of the primary vascular network into a mature hierarchy pattern. ..
  57. Nanduri J, Wang N, Yuan G, Khan S, Souvannakitti D, Peng Y, et al. Intermittent hypoxia degrades HIF-2alpha via calpains resulting in oxidative stress: implications for recurrent apnea-induced morbidities. Proc Natl Acad Sci U S A. 2009;106:1199-204 pubmed publisher
    ..These observations demonstrate that, unlike continuous hypoxia, IH leads to down-regulation of HIF-2alpha via a calpain-dependent signaling pathway and results in oxidative stress as well as autonomic morbidities. ..
  58. Ndubuizu O, Chavez J, Lamanna J. Increased prolyl 4-hydroxylase expression and differential regulation of hypoxia-inducible factors in the aged rat brain. Am J Physiol Regul Integr Comp Physiol. 2009;297:R158-65 pubmed publisher
    ..The posttranslational regulation of HIF-2alpha under normoxic conditions seems to be attenuated in the aged rat brain, which is an in vivo demonstration of differential regulation of HIF-1alpha and HIF-2alpha. ..
  59. Yan Q, Bartz S, Mao M, Li L, Kaelin W. The hypoxia-inducible factor 2alpha N-terminal and C-terminal transactivation domains cooperate to promote renal tumorigenesis in vivo. Mol Cell Biol. 2007;27:2092-102 pubmed
  60. Agrawal A, Gajghate S, Smith H, Anderson D, Albert T, Shapiro I, et al. Cited2 modulates hypoxia-inducible factor-dependent expression of vascular endothelial growth factor in nucleus pulposus cells of the rat intervertebral disc. Arthritis Rheum. 2008;58:3798-808 pubmed publisher
    ..We suggest that the 2 arms of the regulatory circuit serve to maintain survival activities and inhibit angiogenesis in the healthy disc. ..
  61. Naranjo Suarez S, Castellanos M, Alvarez Tejado M, Vara A, Landazuri M, del Peso L. Down-regulation of hypoxia-inducible factor-2 in PC12 cells by nerve growth factor stimulation. J Biol Chem. 2003;278:31895-901 pubmed
    ..Finally, the effect of NGF on HIF2 alpha correlates with reduction of both basal and hypoxia-induced vascular endothelial growth factor mRNA levels...
  62. Park S, Dadak A, Haase V, Fontana L, Giaccia A, Johnson R. Hypoxia-induced gene expression occurs solely through the action of hypoxia-inducible factor 1alpha (HIF-1alpha): role of cytoplasmic trapping of HIF-2alpha. Mol Cell Biol. 2003;23:4959-71 pubmed
  63. Hogenesch J, Chan W, Jackiw V, Brown R, Gu Y, Pray Grant M, et al. Characterization of a subset of the basic-helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway. J Biol Chem. 1997;272:8581-93 pubmed
  64. Rankin E, Biju M, Liu Q, Unger T, Rha J, Johnson R, et al. Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo. J Clin Invest. 2007;117:1068-77 pubmed
    ..of hepatic EPO expression, we have generated mice with conditional inactivation of Hif-1alpha and/or Hif-2alpha (Epas1) in hepatocytes...
  65. Park H, Park J, Kim H, Choi C, Lee H, Kim B, et al. Sildenafil alleviates bronchopulmonary dysplasia in neonatal rats by activating the hypoxia-inducible factor signaling pathway. Am J Respir Cell Mol Biol. 2013;48:105-13 pubmed publisher
    ..This study provides a better understanding about the mode of action for sildenafil, and suggests that HIF can be a potential target for treating patients with BPD. ..
  66. Bai C, Liu X, Liu W, Ma D. Regional expression of the hypoxia-inducible factor (HIF) system and association with cardiomyocyte cell cycle re-entry after myocardial infarction in rats. Heart Vessels. 2008;23:193-200 pubmed publisher
    ..Both HIF subunits might be potent stimuli for cardiomyocytes to re-enter the cell cycle and initiate DNA synthesis. ..
  67. Yuan G, Peng Y, Reddy V, Makarenko V, Nanduri J, Khan S, et al. Mutual antagonism between hypoxia-inducible factors 1? and 2? regulates oxygen sensing and cardio-respiratory homeostasis. Proc Natl Acad Sci U S A. 2013;110:E1788-96 pubmed publisher
  68. Miyashita R, Chen L, Oshiro H, Uchino H, Shibasaki F. Int6 silencing causes induction of angiogenic factors in neuronal cells via accumulation of hypoxia-inducible factor 2? and decreases brain damage in rats. Neurosci Lett. 2012;528:83-8 pubmed publisher
  69. Fujita N, Chiba K, Shapiro I, Risbud M. HIF-1? and HIF-2? degradation is differentially regulated in nucleus pulposus cells of the intervertebral disc. J Bone Miner Res. 2012;27:401-12 pubmed publisher
    ..These results for the first time provide a rationale for the normoxic stabilization as well as the maintenance of steady-state levels of HIF-1? and HIF-2? in nucleus pulposus cells. ..
  70. Woods S, Whitelaw M. Differential activities of murine single minded 1 (SIM1) and SIM2 on a hypoxic response element. Cross-talk between basic helix-loop-helix/per-Arnt-Sim homology transcription factors. J Biol Chem. 2002;277:10236-43 pubmed
  71. Ladoux A, Frelin C. Cardiac expressions of HIF-1 alpha and HLF/EPAS, two basic loop helix/PAS domain transcription factors involved in adaptative responses to hypoxic stresses. Biochem Biophys Res Commun. 1997;240:552-6 pubmed
    Expression of many mammalian genes is regulated by oxygen tension. HIF-1 alpha and HLF/EPAS are two basic helix-loop-helix/PAS domain transcription factors that bind to hypoxia sensitive elements in the promoters /enhancers of hypoxia ..
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    ..Future studies will address whether the molecular abnormalities described in this study are directly responsible for the retinal disease in HIF-2alpha-KO mice. ..
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    ..These data demonstrate that dysregulation of intestinal hypoxia and HIF2α signaling is critical for progressive iron overload in β-thalassemia and may be a novel therapeutic target in several anemic iron-overload disorders. ..