Journal of Isfahan Medical School

Journal of Isfahan Medical School

A Comprehensive Review on Environmental and Microenvironmental Oxygen Sensing Pathways Mediated by Hypoxia-Inducible Factors (HIFs)

Document Type : Review Article

Authors
Fatemeh Choopani 1
Ali Choopani 2
Mahmood Tavallaei 3
Nasrin Kariminejad 1
1 Human Genetics Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
2 PhD in Biochemistry, Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
3 Professor, Human Genetics Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
10.22122/jims.v37i520.11114
Abstract
Oxygen deficiency, referred to as hypoxia, can be divided into two categories of environmental (exogenous) which is sensitized by respiratory cells, and microenvironmental (endogenous) responses by other cells in the body, like cancer cells. Cell responses to oxygen fluctuations are mediated by hypoxia-inducible factors (HIFs). Lung is known as the first organ that encounters the exogenous and environmental oxygen after breathing. However, data are limited for HIF respiratory pathways of environmental oxygen sensing inside the lung cells. Thus, we evaluated the role of both HIF-1 and HIF-2 isoforms in environmental hypoxia sensation by pulmonary vascular and bronchial cells. Then, we introduced the role of HIFs in microenvironmental and endogenous oxygen sensation in tissues and cells other than respiratory cells as well as all of involved molecular mechanisms in those non-lung cells and tissues. Next, a detailed emphasize was put on the strict role of HIF molecule in tumor cells and cancer stem cells.
Keywords
Hypoxia
Hypoxia-inducible factor 1
Hypoxia-inducible factor 2
Lung
Cancer
  1. Semenza, G.L., Oxygen sensing, hypoxia-inducible factors, and disease pathophysiology. Annual Review of Pathology: Mechanisms of Disease, 2014. 9: p. 47-71.
  2. Semenza, G.L., Hypoxia-inducible factors in physiology and medicine. Cell, 2012. 148(3): p. 399-408.
  3. Keith, B., R.S. Johnson, and M.C. Simon, HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression. Nature Reviews Cancer, 2012. 12(1): p. 9.
  4. Scholz, C.C. and C.T. Taylor, Targeting the HIF pathway in inflammation and immunity. Current opinion in pharmacology, 2013. 13(4): p. 646-653.
  5. Vaupel, P. and A. Mayer, Hypoxia in tumors: pathogenesis-related classification, characterization of hypoxia subtypes, and associated biological and clinical implications, in Oxygen Transport to Tissue XXXVI. 2014, Springer. p. 19-24.
  6. Zhou, J., et al., Tumor hypoxia and cancer progression. Cancer letters, 2006. 237(1): p. 10-21.
  7. Zhong, H., et al., Overexpression of hypoxia-inducible factor 1α in common human cancers and their metastases. Cancer research, 1999. 59(22): p. 5830-5835.
  8. Compernolle, V., et al., Loss of HIF-2α and inhibition of VEGF impair fetal lung maturation, whereas treatment with VEGF prevents fatal respiratory distress in premature mice. Nature medicine, 2002. 8(7): p. 702.
  9. Mimeault, M. and S.K. Batra, Hypoxia‐inducing factors as master regulators of stemness properties and altered metabolism of cancer‐and metastasis‐initiating cells. Journal of cellular and molecular medicine, 2013. 17(1): p. 30-54.
  10. Dai, Z., et al., PHD2 Deficiency in endothelial cells and hematopoietic cells induces obliterative vascular remodeling and severe pulmonary arterial hypertension in mice and humans through HIF-2α. Circulation, 2016: p. CIRCULATIONAHA. 116.021494.
  11. Bonnet, D. and J.E. Dick, Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nature medicine, 1997. 3(7): p. 730.
  12. Wang, Y., et al., Targeting HIF1α eliminates cancer stem cells in hematological malignancies. Cell stem cell, 2011. 8(4): p. 399-411.
  13. Wagner, K.F., et al., Hypoxia-induced mitogenic factor has antiapoptotic action and is upregulated in the developing lung: coexpression with hypoxia-inducible factor-2α. American journal of respiratory cell and molecular biology, 2004. 31(3): p. 276-282.
  14. Schmelzle, T. and M.N. Hall, TOR, a central controller of cell growth. Cell, 2000. 103(2): p. 253-262.
  15. Feldser, D., et al., Reciprocal positive regulation of hypoxia-inducible factor 1α and insulin-like growth factor 2. Cancer research, 1999. 59(16): p. 3915-3918.
  16. Jiang, B.-H., et al., 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 research, 1997. 57(23): p. 5328-5335.
  17. McMahon, S., et al., Transforming growth factor β1 induces hypoxia-inducible factor-1 stabilization through selective inhibition of PHD2 expression. Journal of Biological Chemistry, 2006. 281(34): p. 24171-24181.
  18. Nishi, H., et al., Hypoxia-inducible factor-1 transactivates transforming growth factor-β3 in trophoblast. Endocrinology, 2004. 145(9): p. 4113-4118.
  19. Copple, B.L., Hypoxia stimulates hepatocyte epithelial to mesenchymal transition by hypoxia‐inducible factor and transforming growth factor‐β‐dependent mechanisms. Liver International, 2010. 30(5): p. 669-682.
  20. Schwab, L.P., et al., Hypoxia-inducible factor 1α promotes primary tumor growth and tumor-initiating cell activity in breast cancer. Breast Cancer Research, 2012. 14(1): p. R6.
  21. Weir, E.K., et al., Acute oxygen-sensing mechanisms. New England Journal of Medicine, 2005. 353(19): p. 2042-2055.
  22. Alvanegh, A.G., et al., Decreased expression of miR-20a and miR-92a in the serum from sulfur mustard-exposed patients during the chronic phase of resulting illness. Inhalation toxicology, 2015. 27(13): p. 682-688.
  23. Ghorbani Alvanegh, A., M. Tavallaei, and H. Edalat, Evaluating the Epigenetic Effects of the miR17/92 Cluster in Noninvasive Screening of Genetically-Based Respiratory Diseases. Journal of Military Medicine, 2018. 20(1): p. 116-126.
  24. Edalat, H., Cell therapy and Gene therapy of Spinal Cord Injury. Journal of Isfahan Medical School, 2018. Accepted. [in editing]
  25. Edalat, H., M. Sadeghizadeh, and M. Jamali Zavareh, Codon 12 K-ras mutation detection in Iranian patients with colorectal cancer using PCR-RFLP method. Modares Journal of Medical Sciences 2006. 9: p. 33-38.
  26. Ansari, M.H., et al., Deregulation of miR-93 and miR-143 in human esophageal cancer. Tumor Biology, 2016. 37(3): p. 3097-3103.
  27. Hosseini, S.M., et al., Clinically Significant Dysregulation of hsa-miR-30d-5p and hsa-let-7b Expression in Patients with Surgically Resected Non-Small Cell Lung Cancer. Avicenna journal of medical biotechnology, 2018. 10(2): p. 98.
  28. Edalat, H., et al., p75NTR suppression in rat bone marrow stromal stem cells significantly reduced their rate of apoptosis during neural differentiation. Neuroscience letters, 2011. 498(1): p. 15-19.
  29. Edalat, H., et al., Transplanting p75-suppressed bone marrow stromal cells promotes functional behavior in a rat model of spinal cord injury. Iranian biomedical journal, 2013. 17(3): p. 140.
  30. Chen, X., et al., Cold inducible RNA binding protein is involved in chronic hypoxia induced neuron apoptosis by down-regulating HIF-1α expression and regulated by microRNA-23a. International journal of biological sciences, 2017. 13(4): p. 518.
  31. Bruick, R.K. and S.L. McKnight, A conserved family of prolyl-4-hydroxylases that modify HIF. Science, 2001. 294(5545): p. 1337-1340.
  32. Epstein, A.C., et al., C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell, 2001. 107(1): p. 43-54.
  33. Ivan, M., et al., HIFα targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science, 2001. 292(5516): p. 464-468.
  34. Jaakkola, P., et al., Targeting of HIF-α to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science, 2001. 292(5516): p. 468-472.
  35. Kaelin Jr, W.G. and P.J. Ratcliffe, Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Molecular cell, 2008. 30(4): p. 393-402.
  36. Wang, G.L., et al., Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proceedings of the national academy of sciences, 1995. 92(12): p. 5510-5514.
  37. Bradford, J.R. and H.P. Dean, The Pulmonary Circulation 1. The Journal of physiology, 1894. 16(1-2): p. 34-158.
  38. Yu, A.Y., et al., Temporal, spatial, and oxygen-regulated expression of hypoxia-inducible factor-1 in the lung. American Journal of Physiology-Lung Cellular and Molecular Physiology, 1998. 275(4): p. L818-L826.
  39. Hoeper, M.M., et al., Definitions and diagnosis of pulmonary hypertension. Journal of the American College of Cardiology, 2013. 62(25 Supplement): p. D42-D50.
  40. Galiè, N., et al., 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the joint task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). European heart journal, 2015. 37(1): p. 67-119.
  41. Hoeper, M.M., et al., Treatment of pulmonary hypertension. The Lancet Respiratory Medicine, 2016. 4(4): p. 323-336.
  42. Stenmark, K.R., K.A. Fagan, and M.G. Frid, Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms. Circulation research, 2006. 99(7): p. 675-691.
  43. Ball, M.K., et al., Regulation of hypoxia-induced pulmonary hypertension by vascular smooth muscle hypoxia-inducible factor-1α. American journal of respiratory and critical care medicine, 2014. 189(3): p. 314-324.
  44. Bogaard, H.J., et al., Chronic pulmonary artery pressure elevation is insufficient to explain right heart failure. Circulation, 2009. 120(20): p. 1951-1960.
  45. Kim, Y.-M., et al., Hypoxia inducible factor-1α in pulmonary artery smooth muscle cells lowers vascular tone by decreasing myosin light chain phosphorylation. Circulation research, 2013: p. CIRCRESAHA. 112.300646.
  46. Sheikh, A.Q., et al., Smooth muscle cell progenitors are primed to muscularize in pulmonary hypertension. Science translational medicine, 2015. 7(308): p. 308ra159-308ra159.
  47. Sheikh, A.Q., et al., Cell Autonomous and Non-cell Autonomous Regulation of SMC Progenitors in Pulmonary Hypertension. Cell reports, 2018. 23(4): p. 1152-1165.
  48. Smith, K.A. and J.X.-J. Yuan, Hypoxia-inducible factor-1α in pulmonary arterial smooth muscle cells and hypoxia-induced pulmonary hypertension. 2014, American Thoracic Society.
  49. Cowburn, A.S., et al., HIF2α–arginase axis is essential for the development of pulmonary hypertension. Proceedings of the National Academy of Sciences, 2016. 113(31): p. 8801-8806.
  50. Böhm, F. and J. Pernow, The importance of endothelin-1 for vascular dysfunction in cardiovascular disease. Cardiovascular research, 2007. 76(1): p. 8-18.
  51. Torres-Capelli, M., et al., Role of Hif2α oxygen sensing pathway in bronchial epithelial club cell proliferation. Scientific reports, 2016. 6: p. 25357.
  52. Fang, C., et al., Resistin-like molecule-β is a human airway remodelling mediator. European Respiratory Journal, 2012. 39(2): p. 458-466.
  53. Elorza, A., et al., HIF2α acts as an mTORC1 activator through the amino acid carrier SLC7A5. Molecular cell, 2012. 48(5): p. 681-691.
  54. Sonenberg, N. and A.G. Hinnebusch, Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell, 2009. 136(4): p. 731-745.
  55. Ustiyan, V., et al., Foxm1 transcription factor is critical for proliferation and differentiation of Clara cells during development of conducting airways. Developmental biology, 2012. 370(2): p. 198-212.
  56. Hodson, E.J., et al., Regulation of ventilatory sensitivity and carotid body proliferation in hypoxia by the PHD2/HIF‐2 pathway. The Journal of physiology, 2016. 594(5): p. 1179-1195.
  57. Macias, D., et al., HIF-2α is essential for carotid body development and function. eLife, 2018. 7: p. e34681.
  58. Angelini, D.J., et al., Hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMα) induces the vascular and hemodynamic changes of pulmonary hypertension. American Journal of Physiology-Lung Cellular and Molecular Physiology, 2009. 296(4): p. L582-L593.
  59. Yu, S., et al., Role of diabetes in the development of acute respiratory distress syndrome. Critical care medicine, 2013. 41(12): p. 2720.
  60. Tabibiazar, R. and S.V. Edelman, Silent ischemia in people with diabetes: a condition that must be heard. Clinical Diabetes, 2003. 21(1): p. 5-9.
  61. Lamouille, S., J. Xu, and R. Derynck, Molecular mechanisms of epithelial–mesenchymal transition. Nature reviews Molecular cell biology, 2014. 15(3): p. 178.
  62. Krishnamachary, B., et al., Hypoxia-inducible factor-1-dependent repression of E-cadherin in von Hippel-Lindau tumor suppressor–null renal cell carcinoma mediated by TCF3, ZFHX1A, and ZFHX1B. Cancer research, 2006. 66(5): p. 2725-2731.
  63. Zhang, Q., et al., Wnt/β-catenin signaling enhances hypoxia-induced epithelial–mesenchymal transition in hepatocellular carcinoma via crosstalk with hif-1α signaling. Carcinogenesis, 2013. 34(5): p. 962-973.
  64. Lin, G., et al., The dual PI3K/mTOR inhibitor NVP-BEZ235 prevents epithelial–mesenchymal transition induced by hypoxia and TGF-β1. European journal of pharmacology, 2014. 729: p. 45-53.
  65. Al-Hajj, M., et al., Prospective identification of tumorigenic breast cancer cells. Proceedings of the National Academy of Sciences, 2003. 100(7): p. 3983-3988.
  66. Philip, B., et al., HIF expression and the role of hypoxic microenvironments within primary tumours as protective sites driving cancer stem cell renewal and metastatic progression. Carcinogenesis, 2013. 34(8): p. 1699-1707.
  67. Bhaskara, V.K., et al., Intermittent hypoxia regulates stem-like characteristics and differentiation of neuroblastoma cells. PloS one, 2012. 7(2): p. e30905.
  68. Miao, Z.-F., et al., Influence of different hypoxia models on metastatic potential of SGC-7901 gastric cancer cells. Tumor Biology, 2014. 35(7): p. 6801-6808.
  69. Zhu, H., et al., Upregulation of autophagy by hypoxia-inducible factor-1α promotes EMT and metastatic ability of CD133+ pancreatic cancer stem-like cells during intermittent hypoxia. Oncology reports, 2014. 32(3): p. 935-942.
  70. Luo, Y., et al., Cells susceptible to epithelial-mesenchymal transition are enriched in stem-like side population cells from prostate cancer. Oncology reports, 2014. 31(2): p. 874-884.
  71. Giannoni, E., M. Parri, and P. Chiarugi, EMT and oxidative stress: a bidirectional interplay affecting tumor malignancy. Antioxidants & redox signaling, 2012. 16(11): p. 1248-1263.
  72. Nishi, K., et al., LPS induces hypoxia-inducible factor 1 activation in macrophage-differentiated cells in a reactive oxygen species–dependent manner. Antioxidants & redox signaling, 2008. 10(5): p. 983-996.
  73. Cho, K.H., et al., A ROS/STAT3/HIF‐1α signaling cascade mediates EGF‐induced TWIST1 expression and prostate cancer cell invasion. The Prostate, 2014. 74(5): p. 528-536.
  74. Calvani, M., et al., Time-dependent stabilization of hypoxia inducible factor-1α by different intracellular sources of reactive oxygen species. PloS one, 2012. 7(10): p. e38388.
  75. Seebacher, N., D. Richardson, and P. Jansson, Glucose modulation induces reactive oxygen species and increases P‐glycoprotein‐mediated multidrug resistance to chemotherapeutics. British journal of pharmacology, 2015. 172(10): p. 2557-2572.
  76. Shimojo, Y., et al., Attenuation of reactive oxygen species by antioxidants suppresses hypoxia-induced epithelial-mesenchymal transition and metastasis of pancreatic cancer cells. Clinical & experimental metastasis, 2013. 30(2): p. 143-154.
Journal of Isfahan Medical School
Volume 37, Issue 520 - Serial Number 520
January and February 2019
Pages 278-287

  • Receive Date 04 December 2018
  • Accept Date 06 April 2022