Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지
DOI QR코드

DOI QR Code

Involvement of HIF-1α in UVB-Induced Epidermal Hyperplasia

  • Cho, Young-Suk (Department of Pharmacology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine) ;
  • Kim, Chan-Hyung (Department of Pharmacology, Chungbuk National University College of Medicine) ;
  • Park, Jong-Wan (Department of Pharmacology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine)
  • Received : 2009.06.25
  • Accepted : 2009.09.14
  • Published : 2009.12.31
⟨ Previous Next ⟩

Abstract

Keratinocyte overgrowth after UVB exposure is believed to contribute to skin photoageing and cancer development. However, little is known about the transcription factors that epigenetically regulate keratinocyte response to UVB. Recently, $HIF-1{\alpha}$ was found to play a role in epidermal homeostasis by controlling the keratinocyte cell cycle, and thus, we hypothesized that $HIF-1{\alpha}$ is involved in UVB-induced keratinocyte growth. In cultured keratinocytes, $HIF-1{\alpha}$ was found to be down-regulated shortly after UVB exposure and to be involved in UVB-induced proliferation. In mice repeatedly treated with UVB, the epidermis became hyperplasic and keratinocytes lacked $HIF-1{\alpha}$ in nuclei. Based on these results, we suggest that the deregulation of $HIF-1{\alpha}$ is associated with UVB-induced hyperplasia of the epidermis. This work provides insight of the molecular mechanism underlying UV-induced photoageing and skin cancer development.

Keywords

Acknowledgement

Supported by : Korea Health Industry Development Institute

References

  1. Arsham, A.M., Plas, D.R., Thompson, C.B., and Simon, M.C. (2002). Phosphatidylinositol 3-kinase/Akt signaling is neither required for hypoxic stabilization of HIF-1 alpha nor sufficient for HIF-1-dependent target gene transcription. J. Biol. Chem. 277, 15162-15170 https://doi.org/10.1074/jbc.M111162200
  2. Cho, Y.S., Bae, J.M., Chun, Y.S., Chung, J.H., Jeon, Y.K., Kim, I.S., Kim, M.S., and Park, J.W. (2008). HIF-1alpha controls keratinocyte proliferation by up-regulating p21(WAF1/Cip1). Biochim. Biophys. Acta 1783, 323-333 https://doi.org/10.1016/j.bbamcr.2007.11.017
  3. Chun, Y.S., Choi, E., Kim, G.T., Lee, M.J., Lee, M.J., Lee, S.E., Kim, M.S., and Park, J.W. (2000). Zinc induces the accumulation of hypoxia-inducible factor (HIF)-1alpha, but inhibits the nuclear translocation of HIF-1beta, causing HIF-1 inactivation. Biochem. Biophys. Res. Commun. 268, 652-656 https://doi.org/10.1006/bbrc.2000.2180
  4. El-Abaseri, T.B., Putta, S., and Hansen, L.A. (2006). Ultraviolet irradiation induces keratinocyte proliferation and epidermal hyperplasia through the activation of the epidermal growth factor receptor. Carcinogenesis 27, 225-231 https://doi.org/10.1093/carcin/bgi220
  5. Gerald, D., Berra, E., Frapart, Y.M., Chan, D.A., Giaccia, A.J., Mansuy, D., Pouyssegur, J., Yaniv, M., and Mechta-Grigoriou, F. (2004) JunD reduces tumor angiogenesis by protecting cells from oxidative stress. Cell 118, 781-794 https://doi.org/10.1016/j.cell.2004.08.025
  6. Huang, L.E. (2008). Carrot and stick: HIF-alpha engages c-Myc in hypoxic adaptation. Cell Death Differ. 15, 672-677 https://doi.org/10.1038/sj.cdd.4402302
  7. Hudson, C.C., Liu, M., Chiang, G.G., Otterness, D.M., Loomis, D.C., Kaper, F., Giaccia, A.J., and Abraham, R.T. (2002). Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin. Mol. Cell. Biol. 22, 7004- 7014 https://doi.org/10.1128/MCB.22.20.7004-7014.2002
  8. Iyer, N.V., Kotch, L.E., Agani, F., Leung, S.W., Laughner, E., Wenger, R.H., Gassmann, M., Gearhart, J.D., Lawler, A.M., Yu, A.Y., et al. (1998). Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha. Genes Dev. 12, 149-162 https://doi.org/10.1101/gad.12.2.149
  9. Kaidi, A., Williams, A.C., and Paraskeva, C. (2007). Interaction between beta-catenin and HIF-1 promotes cellular adaptation to hypoxia. Nat. Cell Biol. 9, 210-217 https://doi.org/10.1038/ncb1534
  10. Kim, H.L., Cho, Y.S., Choi, H., Chun, Y.S., Lee, Z.H., and Park, J.W. (2009). Hypoxia-inducible factor 1alpha is deregulated by the serum of rats with adjuvant-induced arthritis. Biochem. Biophys. Res. Commun. 378, 123-128 https://doi.org/10.1016/j.bbrc.2008.11.013
  11. Koshiji, M., Kageyama, Y., Pete, E.A., Horikawa, I., Barrett, J.C., and Huang, L.E. (2004). HIF-1alpha induces cell cycle arrest by functionally counteracting Myc. EMBO J. 23, 1949-1956 https://doi.org/10.1038/sj.emboj.7600196
  12. Lang, K.J., Kappel, A., and Goodall, G.J. (2002). Hypoxia-inducible factor-1alpha mRNA contains an internal ribosome entry site that allows efficient translation during normoxia and hypoxia. Mol. Biol. Cell 13, 1792-1801 https://doi.org/10.1091/mbc.02-02-0017
  13. Lee, J.K., Kim, J.H., Nam, K.T., and Lee, S.H. (2003). Molecular events associated with apoptosis and proliferation induced by ultraviolet-B radiation in the skin of hairless mice. J. Dermatol. Sci. 32, 171-179 https://doi.org/10.1016/S0923-1811(03)00094-X
  14. Lim, J.H., Chun, Y.S., and Park, J.W. (2008). Hypoxia-inducible factor-1alpha obstructs a Wnt signaling pathway by inhibiting the hARD1-mediated activation of beta-catenin. Cancer Res. 68, 5177-5184 https://doi.org/10.1158/0008-5472.CAN-07-6234
  15. Marrot, L., and Meunier, J.R. (2008). Skin DNA photodamage and its biological consequences. J. Am. Acad. Dermatol. 58, S139- S148 https://doi.org/10.1016/j.jaad.2007.12.007
  16. Matsumura, Y., and Ananthaswamy, H.N. (2002). Molecular mechanisms of photocarcinogenesis. Front. Biosci. 7, d765-d783 https://doi.org/10.2741/matsumur
  17. Melnikova, V.O., and Ananthaswamy, H.N. (2005). Cellular and molecular events leading to the development of skin cancer. Mutat. Res. 571, 91-106 https://doi.org/10.1016/j.mrfmmm.2004.11.015
  18. Ouhtit, A., Muller, H.K., Davis, D.W., Ullrich, S.E., McConkey, D., and Ananthaswamy, H.N. (2000). Temporal events in skin injury and the early adaptive responses in ultraviolet-irradiated mouse skin. Am. J. Pathol. 156, 201-207 https://doi.org/10.1016/S0002-9440(10)64720-7
  19. Park, H. (1999). Aromatic hydrocarbon nuclear translocator as a common component for the hypoxia- and dioxin-induced gene expression. Mol. Cells 9, 172-178
  20. Peus, D., Meves, A., Vasa, R.A., Beyerle, A., O'Brien, T., and Pittelkow, M.R. (1999). H2O2 is required for UVB-induced EGF receptor and downstream signaling pathway activation. Free Radic. Biol. Med. 27, 1197-1202 https://doi.org/10.1016/S0891-5849(99)00198-7
  21. Rezvani, H.R., Dedieu, S., North, S., Belloc, F., Rossignol, R., Letellier, T., de Verneuil, H., Taieb, A., and Mazurier, F. (2007). Hypoxia-inducible factor-1alpha, a key factor in the keratinocyte response to UVB exposure. J. Biol. Chem. 282, 16413-16422 https://doi.org/10.1074/jbc.M611397200
  22. Schofield, C.J., and Ratcliffe, P.J. (2004). Oxygen sensing by HIF hydroxylases. Nat. Rev. Mol. Cell Biol. 5, 343-354
  23. Wang, G.L., and Semenza, G.L. (1995). Purification and characterization of hypoxia-inducible factor 1. J. Biol. Chem. 270, 1230- 1237 https://doi.org/10.1074/jbc.270.3.1230
  24. Wunderlich, L., Paragh, G., Wikonkal, N.M., Banhegyi, G., Karpati, S., and Mandl, J. (2008). UVB induces a biphasic response of HIF-1alpha in cultured human keratinocytes. Exp. Dermatol. 17, 335-342 https://doi.org/10.1111/j.1600-0625.2007.00640.x
  25. Zhong, H., Chiles, K., Feldser, D., Laughner, E., Hanrahan, C., Georgescu, M.M., Simons, J.W., and Semenza, G.L. (2000). Modulation of hypoxia-inducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/ FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics. Cancer Res. 60, 1541-1545

Cited by

  1. Pyrithione-zinc Prevents UVB-induced Epidermal Hyperplasia by Inducing HIF-$1{\alpha}$ vol.14, pp.2, 2009, https://doi.org/10.4196/kjpp.2010.14.2.91
  2. Sunitinib deregulates tumor adaptation to hypoxia by inhibiting HIF-1α synthesis in HT-29 colon cancer cells vol.398, pp.2, 2009, https://doi.org/10.1016/j.bbrc.2010.06.060
  3. Effects of baicalein and wogonin isolated from Scutellaria baicalensis roots on skin damage in acute UVB-irradiated hairless mice vol.661, pp.1, 2009, https://doi.org/10.1016/j.ejphar.2011.04.033
  4. Uncovering the role of hypoxia inducible factor-1α in skin carcinogenesis vol.1816, pp.1, 2009, https://doi.org/10.1016/j.bbcan.2011.02.001
  5. Protein indicators for HaCaT cell damage induced by UVB irradiation vol.114, pp.None, 2009, https://doi.org/10.1016/j.jphotobiol.2012.05.015
  6. Reversing wrinkled skin and hair loss in mice by restoring mitochondrial function vol.9, pp.7, 2009, https://doi.org/10.1038/s41419-018-0765-9
  7. HOXA9 inhibits HIF-1α-mediated glycolysis through interacting with CRIP2 to repress cutaneous squamous cell carcinoma development vol.9, pp.1, 2009, https://doi.org/10.1038/s41467-018-03914-5