DOI QR코드

DOI QR Code

Overexpression of KAI1 Protein in Diabetic Skin Tissues

  • Cho, Moon Kyun (Department of Dermatology, Soonchunhyang University College of Medicine) ;
  • Kwon, Sun Bum (Department of Dermatology, Soonchunhyang University College of Medicine) ;
  • Kim, Chul Han (Department of Plastic and Reconstructive Surgery, Soonchunhyang University College of Medicine) ;
  • Lee, Yoon-Jin (Soonchunhyung Environmental Health Center for Asbestos, Soonchunhyang University College of Medicine) ;
  • Nam, Hae-Seon (Division of Molecular Cancer Research, Soonchunhyang University College of Medicine) ;
  • Lee, Sang-Han (Division of Molecular Cancer Research, Soonchunhyang University College of Medicine)
  • 투고 : 2013.10.22
  • 심사 : 2013.11.23
  • 발행 : 2014.05.15

초록

Background Patients with diabetes mellitus often have a difficult life, suffering from foot ulceration or amputation. Diabetes is characterized by chronic inflammation, and one of the features of inflammation is hypoxia. Recently, it has been reported that KAI1 is a hypoxia target gene. There is no published research on hypoxia-related KAI1 protein levels in human diabetic skin. Therefore, we have investigated the expression of KAI1 protein in diabetic skin tissue in vivo. Methods The expression of KAI1 protein was evaluated by western blotting in 6 diabetic skin tissue samples and 6 normal skin samples. Immunohistochemical staining was carried out to identify KAI1 expression. Results The western blotting revealed significantly increased expression of the KAI1 protein in diabetic skin tissues as compared to normal skin tissues. Immunohistochemical examination demonstrated that KAI1 was expressed in all diabetic skin tissues with moderate-to-strong positivity and weakly expressed in normal skin tissues. Conclusions Our data suggest that a high expression of the KAI1 protein can be observed in diabetic skin tissue. To the best of our knowledge, this is the first report suggesting that KAI1 protein expression in diabetic skin tissues may be associated with chronic inflammatory states and hypoxia.

키워드

참고문헌

  1. Cheng K, Ho K, Stokes R, et al. Hypoxia-inducible factor-1alpha regulates beta cell function in mouse and human islets. J Clin Invest 2010;120:2171-83. https://doi.org/10.1172/JCI35846
  2. Carroll VA, Ashcroft M. Role of hypoxia-inducible factor (HIF)-1alpha versus HIF-2alpha in the regulation of HIF target genes in response to hypoxia, insulin-like growth factor-I, or loss of von Hippel-Lindau function: implications for targeting the HIF pathway. Cancer Res 2006;66:6264-70. https://doi.org/10.1158/0008-5472.CAN-05-2519
  3. Ahmad FK, He Z, King GL. Molecular targets of diabetic cardiovascular complications. Curr Drug Targets 2005;6: 487-94. https://doi.org/10.2174/1389450054021990
  4. Fraisl P, Aragones J, Carmeliet P. Inhibition of oxygen sensors as a therapeutic strategy for ischaemic and inflammatory disease. Nat Rev Drug Discov 2009;8:139-52. https://doi.org/10.1038/nrd2761
  5. Karhausen J, Haase VH, Colgan SP. Inflammatory hypoxia: role of hypoxia-inducible factor. Cell Cycle 2005;4:256-8.
  6. Costa C, Incio J, Soares R. Angiogenesis and chronic inflammation: cause or consequence? Angiogenesis 2007;10:149-66. https://doi.org/10.1007/s10456-007-9074-0
  7. Semenza GL. Regulation of vascularization by hypoxia-inducible factor 1. Ann N Y Acad Sci 2009;1177:2-8. https://doi.org/10.1111/j.1749-6632.2009.05032.x
  8. Lebel-Binay S, Gil ML, Lagaudriere C, et al. Further characterization of CD82/IA4 antigen (type III surface protein): an activation/differentiation marker of mononuclear cells. Cell Immunol 1994;154:468-83. https://doi.org/10.1006/cimm.1994.1092
  9. Dong JT, Isaacs WB, Isaacs JT. Molecular advances in prostate cancer. Curr Opin Oncol 1997;9:101-7. https://doi.org/10.1097/00001622-199701000-00016
  10. Kim B, Boo K, Lee JS, et al. Identification of the KAI1 metastasis suppressor gene as a hypoxia target gene. Biochem Biophys Res Commun 2010;393:17984.
  11. Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer 2003;3:721-32. https://doi.org/10.1038/nrc1187
  12. White A, Lamb PW, Barrett JC. Frequent downregulation of the KAI1(CD82) metastasis suppressor protein in human cancer cell lines. Oncogene 1998;16:3143-9. https://doi.org/10.1038/sj.onc.1201852
  13. Dong JT, Lamb PW, Rinker-Schaeffer CW, et al. KAI1, a metastasis suppressor gene for prostate cancer on human chromosome 11p11.2. Science 1995;268:884-6. https://doi.org/10.1126/science.7754374
  14. Nagira M, Imai T, Ishikawa I, et al. Mouse homologue of C33 antigen (CD82), a member of the transmembrane 4 superfamily: complementary DNA, genomic structure, and expression. Cell Immunol 1994;157:144-57. https://doi.org/10.1006/cimm.1994.1212
  15. Li HP, Chen X, Li MQ. Gestational diabetes induces chronic hypoxia stress and excessive inflammatory response in murine placenta. Int J Clin Exp Pathol 2013;6:650-9.
  16. Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med 2003;9:677-84. https://doi.org/10.1038/nm0603-677
  17. Ivan M, Kondo K, Yang H, et al. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science 2001;292:464-8. https://doi.org/10.1126/science.1059817
  18. Bruick RK, McKnight SL. A conserved family of prolyl-4-hydroxylases that modify HIF. Science 2001;294:1337-40. https://doi.org/10.1126/science.1066373
  19. Qian D, Lin HY, Wang HM, et al. Normoxic induction of the hypoxic-inducible factor-1 alpha by interleukin-1 beta involves the extracellular signal-regulated kinase 1/2 pathway in normal human cytotrophoblast cells. Biol Reprod 2004; 70:1822-7. https://doi.org/10.1095/biolreprod.103.025031
  20. Kutlu B, Cardozo AK, Darville MI, et al. Discovery of gene networks regulating cytokine-induced dysfunction and apoptosis in insulin-producing INS-1 cells. Diabetes 2003;52: 2701-19. https://doi.org/10.2337/diabetes.52.11.2701

피인용 문헌

  1. Predictive factors for successful limb salvage surgery in diabetic foot patients vol.14, pp.None, 2014, https://doi.org/10.1186/1471-2482-14-113