Table of Contents Author Guidelines Submit a Manuscript
Journal of Diabetes Research
Volume 2015, Article ID 173058, 12 pages
http://dx.doi.org/10.1155/2015/173058
Research Article

Synergistic Activations of REG Iα and REG Iβ Promoters by IL-6 and Glucocorticoids through JAK/STAT Pathway in Human Pancreatic β Cells

Department of Biochemistry, Nara Medical University, Kashihara 634-8521, Japan

Received 10 December 2014; Accepted 26 January 2015

Academic Editor: Shi Fang Yan

Copyright © 2015 Akiyo Yamauchi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. J. Meier, “Beta cell mass in diabetes: a realistic therapeutic target?” Diabetologia, vol. 51, no. 5, pp. 703–713, 2008. View at Publisher · View at Google Scholar · View at Scopus
  2. A. Jurczyk, R. Bortell, and L. C. Alonso, “Human β-cell regeneration: progress, hurdles, and controversy,” Current Opinion in Endocrinology, Diabetes and Obesity, vol. 21, no. 2, pp. 102–108, 2014. View at Publisher · View at Google Scholar · View at Scopus
  3. G. C. Weir and S. Bonner-Weir, “Islet β cell mass in diabetes and how it relates to function, birth, and death,” Annals of the New York Academy of Sciences, vol. 1281, no. 1, pp. 92–105, 2013. View at Publisher · View at Google Scholar · View at Scopus
  4. H. Okamoto and S. Takasawa, “Recent advances in the Okamoto model: The CD38-cyclic ADP-ribose signal system and the regenerating gene protein (Reg)-Reg receptor system in β-cells,” Diabetes, vol. 51, supplement 3, pp. S462–S473, 2002. View at Google Scholar · View at Scopus
  5. S. Takasawa and H. Okamoto, “Pancreatic β-cell death, regeneration and insulin secretion: roles of poly(ADP-ribose) polymerase and cyclic ADP-ribose,” International Journal of Experimental Diabetes Research, vol. 3, no. 2, pp. 79–96, 2002. View at Publisher · View at Google Scholar · View at Scopus
  6. B. Singh, E. Nikoopour, K. Huszarik, J. F. Elliott, and A. M. Jevnikar, “Immunomodulation and regeneration of islet beta cells by cytokines in autoimmune type 1 diabetes,” Journal of Interferon and Cytokine Research, vol. 31, no. 10, pp. 711–719, 2011. View at Publisher · View at Google Scholar · View at Scopus
  7. K. Terazono, H. Yamamoto, S. Takasawa et al., “A novel gene activated in regenerating islets,” The Journal of Biological Chemistry, vol. 263, no. 5, pp. 2111–2114, 1988. View at Google Scholar · View at Scopus
  8. T. Watanabe, Y. Yonemura, H. Yonekura et al., “Pancreatic beta-cell replication and amelioration of surgical diabetes by Reg protein,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 9, pp. 3589–3592, 1994. View at Google Scholar · View at Scopus
  9. J.-L. Liu, W. Cui, B. Li, and Y. Lu, “Possible roles of Reg family proteins in pancreatic islet cell growth,” Endocrine, Metabolic & Immune Disorders: Drug Targets, vol. 8, no. 1, pp. 1–10, 2008. View at Publisher · View at Google Scholar · View at Scopus
  10. A. Parikh, A.-F. Stephan, and E. S. Tzanakakis, “Regenerating proteins and their expression, regulation and signaling,” BioMolecular Concepts, vol. 3, no. 1, pp. 57–70, 2012. View at Publisher · View at Google Scholar
  11. M. Unno, K. Nata, N. Noguchi et al., “Production and characterization of Reg knockout mice: reduced proliferation of pancreatic β-cells in Reg knockout mice,” Diabetes, vol. 51, supplement 3, pp. S478–S483, 2002. View at Google Scholar · View at Scopus
  12. M. Unno, H. Yonekura, K.-I. Nakagawara et al., “Structure, chromosomal localization, and expression of mouse reg genes, reg I and reg II: a novel type of reg gene, reg II, exists in the mouse genome,” The Journal of Biological Chemistry, vol. 268, no. 21, pp. 15974–15982, 1993. View at Google Scholar · View at Scopus
  13. T. Akiyama, S. Takasawa, K. Nata et al., “Activation of Reg gene, a gene for insulin-producing β-cell regeneration: poly(ADP-ribose) polymerase binds Reg promoter and regulates the transcription by autopoly(ADP-ribosyl)ation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 1, pp. 48–53, 2001. View at Publisher · View at Google Scholar · View at Scopus
  14. T. Watanabe, H. Yonekura, K. Terazono, H. Yamamoto, and H. Okamoto, “Complete nucleotide sequence of human reg gene and its expression in normal and tumoral tissues: the reg protein, pancreatic stone protein, and pancreatic thread protein are one and the same product of the gene,” The Journal of Biological Chemistry, vol. 265, no. 13, pp. 7432–7439, 1990. View at Google Scholar · View at Scopus
  15. S. Moriizumi, T. Watanabe, M. Unno et al., “Isolation, structural determination and expression of a novel reg gene, human reg Iβ,” Biochimica et Biophysica Acta, vol. 1217, no. 2, pp. 199–202, 1994. View at Publisher · View at Google Scholar · View at Scopus
  16. C. Lasserre, M.-T. Simon, H. Ishikawa et al., “Structural organization and chromosomal localization of a human gene (HIP/PAP) encoding a C-type lectin overexpressed in primary liver cancer,” European Journal of Biochemistry, vol. 224, no. 1, pp. 29–38, 1994. View at Publisher · View at Google Scholar · View at Scopus
  17. N. J. Dusetti, J.-M. Frigerio, M. F. Fox, D. M. Swallow, J.-C. Dagorn, and J. L. Iovanna, “Molecular cloning, genomic organization, and chromosomal localization of the human pancreatitis-associated protein (PAP) gene,” Genomics, vol. 19, no. 1, pp. 108–114, 1994. View at Publisher · View at Google Scholar · View at Scopus
  18. K. Nata, Y. Liu, L. Xu et al., “Molecular cloning, expression and chromosomal localization of a novel human REG family gene, REG III,” Gene, vol. 340, no. 1, pp. 161–170, 2004. View at Publisher · View at Google Scholar · View at Scopus
  19. J. C. Hartupee, H. Zhang, M. F. Bonaldo, M. B. Soares, and B. K. Dieckgraefe, “Isolation and characterization of a cDNA encoding a novel member of the human regenerating protein family: Reg IV,” Biochimica et Biophysica Acta, vol. 1518, no. 3, pp. 287–293, 2001. View at Publisher · View at Google Scholar · View at Scopus
  20. N. Kobayashi, T. Yuasa, and T. Okitsu, “Regenerative medicine for diabetes mellitus,” Cell Transplantation, vol. 18, no. 5-6, pp. 491–496, 2009. View at Google Scholar · View at Scopus
  21. E. Bernal-Mizrachi, R. N. Kulkarni, D. K. Scott, F. Mauvais-Jarvis, A. F. Stewart, and A. Garcia-Ocaña, “Human β-cell proliferation and intracellular signaling part 2: still driving in the dark without a road map,” Diabetes, vol. 63, no. 3, pp. 819–831, 2014. View at Publisher · View at Google Scholar · View at Scopus
  22. J. T. McCluskey, M. Hamid, H. Guo-Parke, N. H. McClenaghan, R. Gomis, and P. R. Flatt, “Development and functional characterization of insulin-releasing human pancreatic beta cell lines produced by electrofusion,” The Journal of Biological Chemistry, vol. 286, no. 25, pp. 21982–21992, 2011. View at Publisher · View at Google Scholar · View at Scopus
  23. H. Ota, A. Itaya-Hironaka, A. Yamauchi et al., “Pancreatic β cell proliferation by intermittent hypoxia via up-regulation of Reg family genes and HGF gene,” Life Sciences, vol. 93, no. 18-19, pp. 664–672, 2013. View at Publisher · View at Google Scholar · View at Scopus
  24. S. Kumari, I. A. Sammut, and G. I. Giles, “The design of nitric oxide donor drugs: s-nitrosothiol tDodSNO is a superior photoactivated donor in comparison to GSNO and SNAP,” European Journal of Pharmacology, vol. 737, pp. 168–176, 2014. View at Publisher · View at Google Scholar · View at Scopus
  25. M. Nielsen, K. Kaltoft, M. Nordahl et al., “Constitutive activation of a slowly migrating isoform of Stat3 in mycosis fungoides: tyrphostin AG490 inhibits Stat3 activation and growth of mycosis fungoides tumor cell lines,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 13, pp. 6764–6769, 1997. View at Publisher · View at Google Scholar · View at Scopus
  26. A. Yamauchi, I. Takahashi, S. Takasawa et al., “Thiazolidinediones inhibit REG Iα gene transcription in gastrointestinal cancer cells,” Biochemical and Biophysical Research Communications, vol. 379, no. 3, pp. 743–748, 2009. View at Publisher · View at Google Scholar · View at Scopus
  27. K. Yoshimoto, T. Fujimoto, A. Itaya-Hironaka et al., “Involvement of autoimmunity to REG, a regeneration factor, in patients with primary Sjögren's syndrome,” Clinical and Experimental Immunology, vol. 174, no. 1, pp. 1–9, 2013. View at Publisher · View at Google Scholar · View at Scopus
  28. H. Ota, S. Tamaki, A. Itaya-Hironaka et al., “Attenuation of glucose-induced insulin secretion by intermittent hypoxia via down-regulation of CD38,” Life Sciences, vol. 90, no. 5-6, pp. 206–211, 2012. View at Publisher · View at Google Scholar · View at Scopus
  29. S. Takasawa, T. Ikeda, T. Akiyama et al., “Cyclin D1 activation through ATF-2 in Reg-induced pancreatic β-cell regeneration,” FEBS Letters, vol. 580, no. 2, pp. 585–591, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. G. Niu, K. L. Wright, Y. Ma et al., “Role of Stat3 in regulating p53 expression and function,” Molecular and Cellular Biology, vol. 25, no. 17, pp. 7432–7440, 2005. View at Publisher · View at Google Scholar · View at Scopus
  31. K. Nakagawa, S. Takasawa, K. Nata et al., “Prevention of Reg I-induced β-cell apoptosis by IL-6/dexamethasone through activation of HGF gene regulation,” Biochimica et Biophysica Acta, vol. 1833, no. 12, pp. 2988–2995, 2013. View at Publisher · View at Google Scholar · View at Scopus
  32. C. Ishii, S. Kawazu, S. Tomono et al., “Appearance of a regenerating (reg) gene protein in pancreatic islets of remission BB/Wor//Tky rats,” Endocrine Journal, vol. 40, no. 2, pp. 269–273, 1993. View at Publisher · View at Google Scholar · View at Scopus
  33. N. J. Baeza, C. I. Moriscot, W. P. Renaud, H. Okamoto, C. G. Figarella, and B. H. Vialettes, “Pancreatic regenerating gene overexpression in the nonobese diabetic mouse during active diabetogenesis,” Diabetes, vol. 45, no. 1, pp. 67–70, 1996. View at Publisher · View at Google Scholar · View at Scopus
  34. E. Anastasi, E. Ponte, R. Gradini et al., “Expression of Reg and cytokeratin 20 during ductal cell differentiation and proliferation in a mouse model of autoimmune diabetes,” European Journal of Endocrinology, vol. 141, no. 6, pp. 644–652, 1999. View at Publisher · View at Google Scholar · View at Scopus
  35. R. Planas, A. Alba, J. Carrillo et al., “Reg (regenerating) gene overexpression in islets from non-obese diabetic mice with accelerated diabetes: role of IFNβ,” Diabetologia, vol. 49, no. 10, pp. 2379–2387, 2006. View at Publisher · View at Google Scholar · View at Scopus
  36. K. L. A. Souza, E. Gurgul-Convey, M. Elsner, and S. Lenzen, “Interaction between pro-inflammatory and anti-inflammatory cytokines in insulin-producing cells,” Journal of Endocrinology, vol. 197, no. 1, pp. 139–150, 2008. View at Publisher · View at Google Scholar · View at Scopus
  37. M. Cnop, J. C. Hannaert, A. Hoorens, D. L. Eizirik, and D. G. Pipeleers, “Inverse relationship between cytotoxicity of free fatty acids in pancreatic islet cells and cellular triglyceride accumulation,” Diabetes, vol. 50, no. 8, pp. 1771–1777, 2001. View at Publisher · View at Google Scholar · View at Scopus
  38. D. Sommerweiss, T. Gorski, S. Richter, A. Garten, and W. Kiess, “Oleate rescues INS-1E β-cells from palmitate-induced apoptosis by preventing activation of the unfolded protein response,” Biochemical and Biophysical Research Communications, vol. 441, no. 4, pp. 770–776, 2013. View at Publisher · View at Google Scholar · View at Scopus
  39. S. Lenzen, “Oxidative stress: the vulnerable β-cell,” Biochemical Society Transactions, vol. 36, no. 3, pp. 343–347, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. A. S. D. Gul, E. Fadillioglu, I. Karabulut, A. Yesilyurt, and T. Delibasi, “The effects of oral carvacrol treatment against H2O2 induced injury on isolated pancreas islet cells of rats,” Islets, vol. 5, no. 4, pp. 149–155, 2013. View at Publisher · View at Google Scholar · View at Scopus
  41. M. Nakata, N. Uto, I. Maruyama, and T. Yada, “Nitric oxide induces apoptosis via Ca2+-dependent processes in the pancreatic β-cell line MIN6,” Cell Structure and Function, vol. 24, no. 6, pp. 451–455, 1999. View at Publisher · View at Google Scholar · View at Scopus
  42. K.-B. Kwon, E.-K. Kim, J.-G. Lim et al., “Protective effect of Coptidis Rhizoma on S-nitroso-N-acetylpenicillamine (SNAP)-induced apoptosis and necrosis in pancreatic RINm5F cells,” Life Sciences, vol. 76, no. 8, pp. 917–929, 2005. View at Publisher · View at Google Scholar · View at Scopus
  43. H. Yamamoto, Y. Uchigata, and H. Okamoto, “Streptozotocin and alloxan induce DNA strand breaks and poly(ADP-ribose) synthetase in pancreatic islets,” Nature, vol. 294, no. 5838, pp. 284–286, 1981. View at Publisher · View at Google Scholar · View at Scopus
  44. Y. Uchigata, H. Yamamoto, A. Kawamura, and H. Okamoto, “Protection by superoxide dismutase, catalase, and poly(ADP-ribose) synthetase inhibitors against alloxan- and streptozotocin-induced islet DNA strand breaks and against the inhibition of proinsulin synthesis,” The Journal of Biological Chemistry, vol. 257, no. 11, pp. 6084–6088, 1982. View at Google Scholar · View at Scopus
  45. T. Hill, O. Krougly, E. Nikoopour et al., “The involvement of interleukin-22 in the expression of pancreatic beta cell regenerative Reg genes,” Cell Regeneration, vol. 2, no. 1, article 2, 11 pages, 2013. View at Publisher · View at Google Scholar
  46. P. J. Francis, J. L. Southgate, T. J. Wilkin, and A. J. Bone, “Expression of an islet regenerating (reg) gene in isolated rat islets: effects of nutrient and non-nutrient growth factors,” Diabetologia, vol. 35, no. 3, pp. 238–242, 1992. View at Publisher · View at Google Scholar · View at Scopus
  47. N. Yoshino, S. Ishihara, M. A. K. Rumi et al., “Interleukin-8 regulates expression of Reg protein in Helicobacter pylori-infected gastric mucosa,” The American Journal of Gastroenterology, vol. 100, no. 10, pp. 2157–2166, 2005. View at Publisher · View at Google Scholar · View at Scopus
  48. T. Kishimoto, “IL-6: From its discovery to clinical applications,” International Immunology, vol. 22, no. 5, pp. 347–352, 2010. View at Publisher · View at Google Scholar · View at Scopus
  49. H. Cheon, J. Yang, and G. R. Stark, “The functions of signal transducers and activators of transcriptions 1 and 3 as cytokine-inducible proteins,” Journal of Interferon & Cytokine Research, vol. 31, no. 1, pp. 33–40, 2011. View at Publisher · View at Google Scholar · View at Scopus
  50. Y.-W. Zhang, L.-S. Ding, and M.-D. Lai, “Reg gene family and human diseases,” World Journal of Gastroenterology, vol. 9, no. 12, pp. 2635–2641, 2003. View at Google Scholar · View at Scopus
  51. C. X. Jin, T. Hayakawa, S. B. H. Ko, H. Ishiguro, and M. Kitagawa, “Pancreatic stone protein/regenerating protein family in pancreatic and gastrointestinal diseases,” Internal Medicine, vol. 50, no. 15, pp. 1507–1516, 2011. View at Publisher · View at Google Scholar · View at Scopus
  52. N. J. Shervani, S. Takasawa, Y. Uchigata et al., “Autoantibodies to REG, a beta-cell regeneration factor, in diabetic patients,” European Journal of Clinical Investigation, vol. 34, no. 11, pp. 752–758, 2004. View at Publisher · View at Google Scholar · View at Scopus
  53. D. J. Gross, L. Weiss, I. Reibstein et al., “Amelioration of diabetes in nonobese diabetic mice with advanced disease by linomide-induced immunoregulation combined with Reg protein treatment,” Endocrinology, vol. 139, no. 5, pp. 2369–2374, 1998. View at Google Scholar · View at Scopus
  54. A. Sekikawa, H. Fukui, S. Fujii et al., “REG Iα protein may function as a trophic and/or anti-apoptotic factor in the development of gastric cancer,” Gastroenterology, vol. 128, no. 3, pp. 642–653, 2005. View at Publisher · View at Google Scholar · View at Scopus
  55. A. Sekikawa, H. Fukui, S. Fujii et al., “REG Iα protein mediates an anti-apoptotic effect of STAT3 signaling in gastric cancer cells,” Carcinogenesis, vol. 29, no. 1, pp. 76–83, 2008. View at Publisher · View at Google Scholar · View at Scopus
  56. A. Sekikawa, H. Fukui, S. Fujii et al., “Possible role of REG Iα protein in ulcerative colitis and colitic cancer,” Gut, vol. 54, no. 10, pp. 1437–1444, 2005. View at Publisher · View at Google Scholar · View at Scopus
  57. T. Fujimura, T. Fujimoto, A. Itaya-Hironaka et al., “Interleukin-6/Stat pathway is responsible for the induction of REG Iα, a new auto-antigen in Sjögren’s syndrome patients, in salivary duct epithelial cells,” Annals of the Rheumatic Diseases, vol. 73, supplement 2, pp. 865–866, 2014. View at Publisher · View at Google Scholar
  58. D. Sanchez, C. Figarella, S. Marchand-Pinatel, N. Bruneau, and O. Guy-Crotte, “Preferential expression of reg Iβ gene in human adult pancreas,” Biochemical and Biophysical Research Communications, vol. 284, no. 3, pp. 729–737, 2001. View at Publisher · View at Google Scholar · View at Scopus
  59. A. Sekikawa, H. Fukui, K. Suzuki et al., “Involvement of the IL-22/REG Iα axis in ulcerative colitis,” Laboratory Investigation, vol. 90, no. 3, pp. 496–505, 2010. View at Publisher · View at Google Scholar · View at Scopus
  60. B. Sigh, T. Hill, O. Krougly et al., “Role of IL-22 in tissue regeneration in autoimmunity,” The Journal of Immunology, vol. 190, meeting abstract supplement, 195.11, 2013. View at Google Scholar
  61. M. Shioya, A. Andoh, S. Kakinoki, A. Nishida, and Y. Fujiyama, “Interleukin 22 receptor 1 expression in pancreas islets,” Pancreas, vol. 36, no. 2, pp. 197–199, 2008. View at Publisher · View at Google Scholar · View at Scopus