Hypoxia and hypoxia inducible factors: Diverse roles in liver diseases

Hepatology

Volumn 55, Issue 2, 2012, Pages 622-633

  Nath, Bharath ^a   Szabo, Gyongyi ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 (2 AMINO 3 METHOXYPHENYL)CHROMONE; 2 MORPHOLINO 8 PHENYLCHROMONE; ALANINE AMINOTRANSFERASE; BONE MORPHOGENETIC PROTEIN; CERULOPLASMIN; CHOLESTEROL; ERYTHROPOIETIN; HEME OXYGENASE 1; HEPATITIS B VIRUS X PROTEIN; HYPOXIA INDUCIBLE FACTOR; HYPOXIA INDUCIBLE FACTOR 1ALPHA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; IRON; ONCOSTATIN M; OXYGEN; PARACETAMOL; RAPAMYCIN; SALIDROSIDE; SILIBININ; TOLL LIKE RECEPTOR 4; TRIACYLGLYCEROL; VASCULOTROPIN;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALCOHOL LIVER CIRRHOSIS; ALTITUDE DISEASE; ANGIOGENESIS; APOPTOSIS; CARCINOGENESIS; CELL PROLIFERATION; CHOLESTEROL BLOOD LEVEL; COPPER METABOLISM; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DISEASE ASSOCIATION; DISEASE MODEL; DNA BINDING; ENZYME ACTIVATION; GENE TARGETING; GRAFT FAILURE; HEPATITIS C; HUMAN; HYPOXIA; INNATE IMMUNITY; ISCHEMIA; LEUKOCYTE MIGRATION; LIPID STORAGE; LIPOGENESIS; LIVER; LIVER CELL CARCINOMA; LIVER DISEASE; LIVER FIBROSIS; LIVER REGENERATION; MITOCHONDRIAL RESPIRATION; NONALCOHOLIC FATTY LIVER; NONHUMAN; OPEN READING FRAME; OXIDATIVE STRESS; OXYGEN TENSION; PRIORITY JOURNAL; PROTEIN PROCESSING; REPERFUSION INJURY; REVIEW; SLEEP APNEA SYNDROME; TRIACYLGLYCEROL BLOOD LEVEL; TUMOR GROWTH; UPREGULATION; XENOBIOTIC METABOLISM;

ACETAMINOPHEN; ANIMALS; ANOXIA; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1; IMMUNITY, INNATE; LIPID METABOLISM; LIVER; LIVER DISEASES; LIVER REGENERATION; METALS; OXYGEN; REPERFUSION INJURY; SLEEP APNEA, OBSTRUCTIVE;

EID: 84856390541     PISSN: 02709139     EISSN: 15273350     Source Type: Journal    
DOI: 10.1002/hep.25497     Document Type: Review

References (105)

1. Jungermann K, Kietzmann T. Oxygen: modulator of metabolic zonation and disease of the liver. HEPATOLOGY 2000; 31: 255-260.
2. 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: 531-537.
3. Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J, Gaskell SJ, et al. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 2001; 292: 468-472.
4. 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.
5. Dimova EY, Kietzmann T. Hypoxia-inducible factors: post-translational crosstalk of signaling pathways. Methods Mol Biol 2010; 647: 215-236.
6. Benita Y, Kikuchi H, Smith AD, Zhang MQ, Chung DC, Xavier RJ. An integrative genomics approach identifies hypoxia inducible factor-1 (HIF-1)-target genes that form the core response to hypoxia. Nucleic Acids Res 2009; 37: 4587-4602.
7. Dioum EM, Chen R, Alexander MS, Zhang Q, Hogg RT, Gerard RD, et al. Regulation of hypoxia-inducible factor 2alpha signaling by the stress-responsive deacetylase sirtuin 1. Science 2009; 324: 1289-1293.
8. Lehwald N, Tao GZ, Jang KY, Sorkin M, Knoefel WT, Sylvester KG. Wnt-beta-catenin signaling protects against hepatic ischemia and reperfusion injury in mice. Gastroenterology 2010; 141: 707-718, 718 e701-705.
9. Ahn YT, Chua MS, Whitlock JP Jr, Shin YC, Song WH, Kim Y, et al. Rodent-specific hypoxia response elements enhance PAI-1 expression through HIF-1 or HIF-2 in mouse hepatoma cells. Int J Oncol 2010; 37: 1627-1638.
10. Yeligar SM, Machida K, Kalra VK. Ethanol-induced HO-1 and NQO1 are differentially regulated by HIF-1alpha and Nrf2 to attenuate inflammatory cytokine expression. J Biol Chem 2010; 285: 35359-35373.
11. Corpechot C, Barbu V, Wendum D, Kinnman N, Rey C, Poupon R, et al. Hypoxia-induced VEGF and collagen I expressions are associated with angiogenesis and fibrogenesis in experimental cirrhosis. HEPATOLOGY 2002; 35: 1010-1021.
12. Maeno H, Ono T, Dhar DK, Sato T, Yamanoi A, Nagasue N. Expression of hypoxia inducible factor-1alpha during liver regeneration induced by partial hepatectomy in rats. Liver Int 2005; 25: 1002-1009.
13. Redaelli CA, Semela D, Carrick FE, Ledermann M, Candinas D, Sauter B, et al. Effect of vascular endothelial growth factor on functional recovery after hepatectomy in lean and obese mice. J Hepatol 2004; 40: 305-312.
14. Peyssonnaux C, Zinkernagel A, Schuepbach R, Rankin E, Vaulont S, Haase V, et al. Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs). J Clin Invest 2007; 117: 1926.
15. Martin F, Linden T, Katschinski DM, Oehme F, Flamme I, Mukhopadhyay CK, et al. Copper-dependent activation of hypoxia-inducible factor (HIF)-1: implications for ceruloplasmin regulation. Blood 2005; 105: 4613-4619.
16. Roth U, Jungermann K, Kietzmann T. Modulation of glucokinase expression by hypoxia-inducible factor 1 and upstream stimulatory factor 2 in primary rat hepatocytes. Biol Chem 2004; 385: 239-247.
17. Maegdefrau U, Amann T, Winklmeier A, Braig S, Schubert T, Weiss TS, et al. Bone morphogenetic protein 4 is induced in hepatocellular carcinoma by hypoxia and promotes tumour progression. J Pathol 2009; 218: 520-529.
18. Krones A, Jungermann K, Kietzmann T. Cross-talk between the signals hypoxia and glucose at the glucose response element of the L-type pyruvate kinase gene. Endocrinology 2001; 142: 2707-2718.
19. Broughan TA, Naukam R, Tan C, Van De Wiele CJ, Refai H, Teague TK. Effects of hepatic zonal oxygen levels on hepatocyte stress responses. J Surg Res 2008; 145: 150-160.
20. Cursio R, Miele C, Filippa N, Van Obberghen E, Gugenheim J. Liver HIF-1 alpha induction precedes apoptosis following normothermic ischemia-reperfusion in rats. Transplant Proc 2008; 40: 2042.
21. Tamagawa K, Horiuchi T, Uchinami M, Doi K, Yoshida M, Nakamura T, et al. Hepatic ischemia-reperfusion increases vascular endothelial growth factor and cancer growth in rats. J Surg Res 2008; 148: 158-163.
22. Tacchini L, Radice L, Bernelli-Zazzera A. Differential activation of some transcription factors during rat liver ischemia, reperfusion, and heat shock. J Cell Physiol 1999; 180: 255-262.
23. Tacchini L, Fusar Poli D, Bernelli-Zazzera A, Cairo G. Transferrin receptor gene expression and transferrin-bound iron uptake are increased during postischemic rat liver reperfusion. HEPATOLOGY 2002; 36: 103-111.
24. Alchera E, Tacchini L, Imarisio C, Dal Ponte C, De Ponti C, Gammella E, et al. Adenosine-dependent activation of hypoxia-inducible factor-1 induces late preconditioning in liver cells. HEPATOLOGY 2008; 48: 230.
25. Schneider M, Van Geyte K, Fraisl P, Kiss J, Aragones J, Mazzone M, et al. Loss or silencing of the PHD1 prolyl hydroxylase protects livers of mice against ischemia/reperfusion injury. Gastroenterology 2010; 138: 1143-1154 e1141-1142.
26. Tsuchihashi S, Ke B, Kaldas F, Flynn E, Busuttil RW, Briscoe DM, et al. Vascular endothelial growth factor antagonist modulates leukocyte trafficking and protects mouse livers against ischemia/reperfusion injury. Am J Pathol 2006; 168: 695-705.
27. Hoppin AG, Katz ES, Kaplan LM, Lauwers GY. Case records of the Massachusetts General Hospital. Case 31-2006. A 15-year-old girl with severe obesity. N Engl J Med 2006; 355: 1593-1602.
28. Mishra P, Nugent C, Afendy A, Bai C, Bhatia P, Afendy M, et al. Apnoeic-hypopnoeic episodes during obstructive sleep apnoea are associated with histological nonalcoholic steatohepatitis. Liver Int 2008; 28: 1080-1086.
29. Jouet P, Sabate JM, Maillard D, Msika S, Mechler C, Ledoux S, et al. Relationship between obstructive sleep apnea and liver abnormalities in morbidly obese patients: a prospective study. Obes Surg 2007; 17: 478-485.
30. Polotsky VY, Patil SP, Savransky V, Laffan A, Fonti S, Frame LA, et al. Obstructive sleep apnea, insulin resistance, and steatohepatitis in severe obesity. Am J Respir Crit Care Med 2009; 179: 228-234.
31. Tatsumi K, Saibara T. Effects of obstructive sleep apnea syndrome on hepatic steatosis and nonalcoholic steatohepatitis. Hepatol Res 2005; 33: 100-104.
32. Tanne F, Gagnadoux F, Chazouilleres O, Fleury B, Wendum D, Lasnier E, et al. Chronic liver injury during obstructive sleep apnea. HEPATOLOGY 2005; 41: 1290-1296.
33. Savransky V, Nanayakkara A, Vivero A, Li J, Bevans S, Smith PL, et al. Chronic intermittent hypoxia predisposes to liver injury. HEPATOLOGY 2007; 45: 1007-1013.
34. Li J, Grigoryev DN, Ye SQ, Thorne L, Schwartz AR, Smith PL, et al. Chronic intermittent hypoxia upregulates genes of lipid biosynthesis in obese mice. J Appl Physiol 2005; 99: 1643-1648.
35. Savransky V, Bevans S, Nanayakkara A, Li J, Smith PL, Torbenson MS, et al. Chronic intermittent hypoxia causes hepatitis in a mouse model of diet-induced fatty liver. Am J Physiol Gastrointest Liver Physiol 2007; 293: G871-877.
36. Savransky V, Reinke C, Jun J, Bevans-Fonti S, Nanayakkara A, Li J, et al. Chronic intermittent hypoxia and acetaminophen induce synergistic liver injury in mice. Exp Physiol 2009; 94: 228-239.
37. James LP, Donahower B, Burke AS, McCullough S, Hinson JA. Induction of the nuclear factor HIF-1alpha in acetaminophen toxicity: evidence for oxidative stress. Biochem Biophys Res Commun 2006; 343: 171-176.
38. Wu YL, Piao DM, Han XH, Nan JX. Protective effects of salidroside against acetaminophen-induced toxicity in mice. Biol Pharm Bull 2008; 31: 1523-1529.
39. Salhanick SD, Belikoff B, Orlow D, Holt D, Reenstra W, Buras JA. Hyperbaric oxygen reduces acetaminophen toxicity and increases HIF-1alpha expression. Acad Emerg Med 2006; 13: 707-714.
40. Sparkenbaugh EM, Saini Y, Greenwood KK, Lapres JJ, Luyendyk JP, Copple BL, et al. The role of hypoxia inducible factor-1 alpha in acetaminophen hepatotoxicity. J Pharmacol Exp Ther 2011; 338: 492-502.
41. Israel Y, Kalant H, Orrego H, Khanna JM, Videla L, Phillips JM. Experimental alcohol-induced hepatic necrosis: suppression by propylthiouracil. Proc Natl Acad Sci U S A 1975; 72: 1137-1141.
42. Orrego H, Carmichael FJ, Saldivia V, Giles HG, Sandrin S, Israel Y. Ethanol-induced increase in portal blood flow: role of adenosine. Am J Physiol 1988; 254: G495-501.
43. Nath B, Szabo G. Alcohol-induced modulation of signaling pathways in liver parenchymal and nonparenchymal cells: implications for immunity. Semin Liver Dis 2009; 29: 166-177.
44. French SW. The role of hypoxia in the pathogenesis of alcoholic liver disease. Hepatol Res 2004; 29: 69-74.
45. Videla L, Bernstein J, Israel Y. Metabolic alterations produced in the liver by chronic ethanol administration. Increased oxidative capacity. Biochem J 1973; 134: 507-514.
46. Yuki T, Thurman RG. The swift increase in alcohol metabolism. Time course for the increase in hepatic oxygen uptake and the involvement of glycolysis. Biochem J 1980; 186: 119-126.
47. Arteel GE, Raleigh JA, Bradford BU, Thurman RG. Acute alcohol produces hypoxia directly in rat liver tissue in vivo: role of Kupffer cells. Am J Physiol 1996; 271: G494-500.
48. Arteel GE, Iimuro Y, Yin M, Raleigh JA, Thurman RG. Chronic enteral ethanol treatment causes hypoxia in rat liver tissue in vivo. HEPATOLOGY 1997; 25: 920-926.
49. Yin HQ, Je YT, Kim M, Kim JH, Kong G, Kang KS, et al. Analysis of hepatic gene expression during fatty liver change due to chronic ethanol administration in mice. Toxicol Appl Pharmacol 2009; 235: 312-320.
50. Li L, Chen SH, Zhang Y, Yu CH, Li SD, Li YM. Is the hypoxia-inducible factor-1 alpha mRNA expression activated by ethanol-induced injury, the mechanism underlying alcoholic liver disease? Hepatobiliary Pancreat Dis Int 2006; 5: 560-563.
51. Li J, French B, Wu Y, Vanketesh R, Montgomery R, Bardag-Gorce F, et al. Liver hypoxia and lack of recovery after reperfusion at high blood alcohol levels in the intragastric feeding model of alcohol liver disease. Exp Mol Pathol 2004; 77: 184-192.
52. Bailey SM, Mantena SK, Millender-Swain T, Cakir Y, Jhala NC, Chhieng D, et al. Ethanol and tobacco smoke increase hepatic steatosis and hypoxia in the hypercholesterolemic apoE-/-mouse: implications for a "multi-hit" hypothesis of fatty liver disease. Free Radic Biol Med 2009; 46: 928-938.
53. Nath B, Levin I, Csak T, Petrasek J, Mueller C, Kodys K, et al. Hepatocyte-specific hypoxia-inducible factor-1alpha is a determinant of lipid accumulation and liver injury in alcohol-induced steatosis in mice. HEPATOLOGY 2010; 53: 1526-1537.
54. Uesugi T, Froh M, Arteel GE, Bradford BU, Thurman RG. Toll-like receptor 4 is involved in the mechanism of early alcohol-induced liver injury in mice. HEPATOLOGY 2001; 34: 101-108.
55. Scharte M, Han X, Uchiyama T, Tawadrous Z, Delude R, Fink M. LPS increases hepatic HIF-1alpha protein and expression of the HIF-1-dependent gene aldolase A in rats. J Surg Res 2006; 135: 262-267.
56. Blouin CC, Page EL, Soucy GM, Richard DE. Hypoxic gene activation by lipopolysaccharide in macrophages: implication of hypoxia-inducible factor 1alpha. Blood 2004; 103: 1124-1130.
57. Peyssonnaux C, Cejudo-Martin P, Doedens A, Zinkernagel AS, Johnson RS, Nizet V. Cutting edge: essential role of hypoxia inducible factor-1alpha in development of lipopolysaccharide-induced sepsis. J Immunol 2007; 178: 7516-7519.
58. van Uden P, Kenneth N, Rocha S. Regulation of hypoxia-inducible factor-1alpha by NF-kappaB. Biochem J 2008; 412: 477-484.
59. Rius J, Guma M, Schachtrup C, Akassoglou K, Zinkernagel AS, Nizet V, et al. NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. Nature 2008; 453: 807-811.
60. Beraza N, Malato Y, Vander Borght S, Liedtke C, Wasmuth H, Dreano M, et al. Pharmacological IKK2 inhibition blocks liver steatosis and initiation of non-alcoholic steatohepatitis. Gut 2008; 57: 655.
61. Thiel M, Caldwell CC, Kreth S, Kuboki S, Chen P, Smith P, et al. Targeted deletion of HIF-1alpha gene in T cells prevents their inhibition in hypoxic inflamed tissues and improves septic mice survival. PLoS ONE 2007; 2: e853.
62. Wolman M, Cervos-Navarro J, Sampaolo S, Cardesa A. Pathological changes in organs of rats chronically exposed to hypoxia. Development of pulmonary lipidosis. Histol Histopathol 1993; 8: 247-255.
63. Bostrom P, Magnusson B, Svensson PA, Wiklund O, Boren J, Carlsson LM, et al. Hypoxia converts human macrophages into triglyceride-loaded foam cells. Arterioscler Thromb Vasc Biol 2006; 26: 1871-1876.
64. Jiang G, Li T, Qiu Y, Rui Y, Chen W, Lou Y. RNA interference for HIF-1alpha inhibits foam cells formation in vitro. Eur J Pharmacol 2007; 562: 183-190.
65. Wada T, Shimba S, Tezuka M. Transcriptional regulation of the hypoxia inducible factor-2alpha (HIF-2alpha) gene during adipose differentiation in 3T3-L1 cells. Biol Pharm Bull 2006; 29: 49-54.
66. Belanger A, Luo Z, Vincent K, Akita G, Cheng S, Gregory R, et al. Hypoxia-inducible factor 1 mediates hypoxia-induced cardiomyocyte lipid accumulation by reducing the DNA binding activity of peroxisome proliferator-activated receptor alpha/retinoid X receptor. Biochem Biophys Res Commun 2007; 364: 567-572.
67. Furuta E, Pai SK, Zhan R, Bandyopadhyay S, Watabe M, Mo YY, et al. Fatty acid synthase gene is up-regulated by hypoxia via activation of Akt and sterol regulatory element binding protein-1. Cancer Res 2008; 68: 1003-1011.
68. Scortegagna M, Ding K, Oktay Y, Gaur A, Thurmond F, Yan LJ, et al. Multiple organ pathology, metabolic abnormalities and impaired homeostasis of reactive oxygen species in Epas1-/- mice. Nat Genet 2003; 35: 331-340.
69. Park S, Haase V, Johnson R. von Hippel Lindau tumor suppressor regulates hepatic glucose metabolism by controlling expression of glucose transporter 2 and glucose 6-phosphatase. Int J Oncol 2007; 30: 341-348.
70. Rankin EB, Rha J, Selak MA, Unger TL, Keith B, Liu Q, et al. HIF-2 regulates hepatic lipid metabolism. Mol Cell Biol 2009; 29: 4527-4538.
71. Qu A, Taylor M, Xue X, Matsubara T, Metzger D, Chambon P, et al. Hypoxia-inducible transcription factor 2alpha promotes steatohepatitis through augmenting lipid accumulation, inflammation, and fibrosis. HEPATOLOGY 2011; 54: 472-483.
72. Xiong S, She H, Zhang AS, Wang J, Mkrtchyan H, Dynnyk A, et al. Hepatic macrophage iron aggravates experimental alcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol 2008; 295: G512-521.
73. Peyssonnaux C, Zinkernagel AS, Schuepbach RA, Rankin E, Vaulont S, Haase VH, et al. Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs). J Clin Invest 2007; 117: 1926-1932.
74. Yim SH, Shah Y, Tomita S, Morris HD, Gavrilova O, Lambert G, et al. Disruption of the Arnt gene in endothelial cells causes hepatic vascular defects and partial embryonic lethality in mice. HEPATOLOGY 2006; 44: 550-560.
75. Mastrogiannaki M, Matak P, Keith B, Simon MC, Vaulont S, Peyssonnaux C. HIF-2alpha, but not HIF-1alpha, promotes iron absorption in mice. J Clin Invest 2009; 119: 1159-1166.
76. Li Z, Lai Z, Ya K, Fang D, Ho YW, Lei Y, et al. Correlation between the expression of divalent metal transporter 1 and the content of hypoxia-inducible factor-1 in hypoxic HepG2 cells. J Cell Mol Med 2008; 12: 569-579.
77. Moon J, Welch T, Gonzalez F, Copple B. Reduced liver fibrosis in hypoxia-inducible factor-1alpha-deficient mice. Am J Physiol Gastrointest Liver Physiol 2009; 296: G582-592.
78. Copple BL, Bai S, Moon JO. Hypoxia-inducible factor-dependent production of profibrotic mediators by hypoxic Kupffer cells. Hepatol Res 2010; 40: 530-539.
79. Novo E, Cannito S, Zamara E, Valfrè di Bonzo L, Caligiuri A, Cravanzola C, et al. Proangiogenic cytokines as hypoxia-dependent factors stimulating migration of human hepatic stellate cells. Am J Pathol 2007; 170: 1942-1953.
80. Shi YF, Fong CC, Zhang Q, Cheung PY, Tzang CH, Wu RS, et al. Hypoxia induces the activation of human hepatic stellate cells LX-2 through TGF-beta signaling pathway. FEBS Lett 2007; 581: 203-210.
81. Copple BL, Bai S, Burgoon LD, Moon JO. Hypoxia-inducible factor-1alpha regulates the expression of genes in hypoxic hepatic stellate cells important for collagen deposition and angiogenesis. Liver Int 2010; 31: 230-244.
82. Xie H, Song J, Liu K, Ji H, Shen H, Hu S, et al. The expression of hypoxia-inducible factor-1alpha in hepatitis B virus-related hepatocellular carcinoma: correlation with patients' prognosis and hepatitis B virus x protein. Dig Dis Sci 2008; 53: 3225-3233.
83. Han HK, Han CY, Cheon EP, Lee J, Kang KW. Role of hypoxia-inducible factor-alpha in hepatitis-B-virus X protein-mediated MDR1 activation. Biochem Biophys Res Commun 2007; 357: 567-573.
84. Yoo YG, Na TY, Seo HW, Seong JK, Park CK, Shin YK, et al. Hepatitis B virus X protein induces the expression of MTA1 and HDAC1, which enhances hypoxia signaling in hepatocellular carcinoma cells. Oncogene 2008; 27: 3405-3413.
85. Moin SM, Chandra V, Arya R, Jameel S. The hepatitis E virus ORF3 protein stabilizes HIF-1alpha and enhances HIF-1-mediated transcriptional activity through p300/CBP. Cell Microbiol 2009; 11: 1409-1421.
86. Nasimuzzaman M, Waris G, Mikolon D, Stupack D, Siddiqui A. Hepatitis C virus stabilizes hypoxia-inducible factor 1alpha and stimulates the synthesis of vascular endothelial growth factor. J Virol 2007; 81: 10249-10257.
87. Ripoli M, D'Aprile A, Quarato G, Sarasin-Filipowicz M, Gouttenoire J, Scrima R, et al. Hepatitis C virus-linked mitochondrial dysfunction promotes hypoxia-inducible factor 1 alpha-mediated glycolytic adaptation. J Virol 2010; 84: 647-660.
88. Olazabal IM, Munoz JA, Rodriguez-Navas C, Alvarez L, Delgado-Baeza E, Garcia-Ruiz JP. Prolactin's role in the early stages of liver regeneration in rats. J Cell Physiol 2009; 219: 626-633.
89. Ren P, Kang Z, Gu G, Liu Y, Xu W, Tao H, et al. Hyperbaric oxygen preconditioning promotes angiogenesis in rat liver after partial hepatectomy. Life Sci 2008; 83: 236-241.
90. Tajima T, Goda N, Fujiki N, Hishiki T, Nishiyama Y, Senoo-Matsuda N, et al. HIF-1alpha is necessary to support gluconeogenesis during liver regeneration. Biochem Biophys Res Commun 2009; 387: 789-794.
91. Vollmer S, Kappler V, Kaczor J, Flugel D, Rolvering C, Kato N, et al. Hypoxia-inducible factor 1alpha is up-regulated by oncostatin M and participates in oncostatin M signaling. HEPATOLOGY 2009; 50: 253-260.
92. Nakamura K, Zen Y, Sato Y, Kozaka K, Matsui O, Harada K, et al. Vascular endothelial growth factor, its receptor Flk-1, and hypoxia inducible factor-1alpha are involved in malignant transformation in dysplastic nodules of the liver. Hum Pathol 2007; 38: 1532-1546.
93. Tanaka H, Yamamoto M, Hashimoto N, Miyakoshi M, Tamakawa S, Yoshie M, et al. Hypoxia-independent overexpression of hypoxia-inducible factor 1alpha as an early change in mouse hepatocarcinogenesis. Cancer Res 2006; 66: 11263-11270.
94. Sun X, Jiang H, Jiang X, Tan H, Meng Q, Sun B, et al. Antisense hypoxia-inducible factor-1alpha augments transcatheter arterial embolization in the treatment of hepatocellular carcinomas in rats. Hum Gene Ther 2009; 20: 314-324.
95. Ryu SH, Chung YH, Lee H, Kim JA, Shin HD, Min HJ, et al. Metastatic tumor antigen 1 is closely associated with frequent postoperative recurrence and poor survival in patients with hepatocellular carcinoma. HEPATOLOGY 2008; 47: 929-936.
96. Bangoura G, Yang L, Huang G, Wang W. Expression of HIF-2alpha/EPAS1 in hepatocellular carcinoma. World J Gastroenterol WJG 2004; 10: 525-530.
97. Bangoura G, Liu Z, Qian Q, Jiang C, Yang G, Jing S. Prognostic significance of HIF-2alpha/EPAS1 expression in hepatocellular carcinoma. World J Gastroenterol WJG 2007; 13: 3176-3182.
98. Dai CX, Gao Q, Qiu SJ, Ju MJ, Cai MY, Xu YF, et al. Hypoxia-inducible factor-1 alpha, in association with inflammation, angiogenesis and MYC, is a critical prognostic factor in patients with HCC after surgery. BMC Cancer 2009; 9: 418.
99. Daskalow K, Rohwer N, Raskopf E, Dupuy E, Kuhl A, Loddenkemper C, et al. Role of hypoxia-inducible transcription factor 1alpha for progression and chemosensitivity of murine hepatocellular carcinoma. J Mol Med 2010; 88: 817-827.
100. Simon F, Bockhorn M, Praha C, Baba HA, Broelsch CE, Frilling A, Weber F. Deregulation of HIF1-alpha and hypoxia-regulated pathways in hepatocellular carcinoma and corresponding non-malignant liver tissue-influence of a modulated host stroma on the prognosis of HCC. Langenbecks Arch Surg 2010; 395: 395-405.
101. Fu J, Chen Y, Cao J, Luo T, Qian YW, Yang W, et al. p28GANK overexpression accelerates hepatocellular carcinoma invasiveness and metastasis via phosphoinositol 3-kinase/AKT/hypoxia-inducible factor-1alpha pathways. HEPATOLOGY 2010; 53: 181-192.
102. Greenberger L, Horak I, Filpula D, Sapra P, Westergaard M, Frydenlund H, et al. A RNA antagonist of hypoxia-inducible factor-1alpha, EZN-2968, inhibits tumor cell growth. Mol Cancer Ther 2008; 7: 3598-3608.
103. Liu F, Wang P, Jiang X, Tan G, Qiao H, Jiang H, et al. Antisense hypoxia-inducible factor 1alpha gene therapy enhances the therapeutic efficacy of doxorubicin to combat hepatocellular carcinoma. Cancer Sci 2008; 99: 2055-2061.
104. Wang W, Jia W, Xu G, Wang Z, Li J, Ma J, et al. Antitumoral activity of rapamycin mediated through inhibition of HIF-1alpha and VEGF in hepatocellular carcinoma. Dig Dis Sci 2008; 54: 2128-2136.
105. García-Maceira P, Mateo J. Silibinin inhibits hypoxia-inducible factor-1alpha and mTOR/p70S6K/4E-BP1 signalling pathway in human cervical and hepatoma cancer cells: implications for anticancer therapy. Oncogene 2009; 28: 313-324.