DOI QR코드

DOI QR Code

Identification of Lactoferrin as a Human Dedifferentiation Factor Through the Studies of Reptile Tissue Regeneration Mechanisms

  • Bae, Kil Soo (Department of Biological Science, Dong-A University) ;
  • Kim, Sun Young (Research Center for Integrative Cellulomics, Korea Research Institute of Bioscience and Biotechnology) ;
  • Park, Soon Yong (Department of Biological Science, Dong-A University) ;
  • Jeong, Ae Jin (Department of Biological Science, Dong-A University) ;
  • Lee, Hyun Hee (Department of Biological Science, Dong-A University) ;
  • Lee, Jungwoon (Regenerative Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Cho, Yee Sook (Regenerative Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Leem, Sun-Hee (Department of Biological Science, Dong-A University) ;
  • Kang, Tae-Hong (Department of Biological Science, Dong-A University) ;
  • Bae, Kwang-Hee (Research Center for Integrative Cellulomics, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Jae Ho (Medical Research Center for Ischemic Tissue Regeneration, Pusan National University) ;
  • Jung, Yong Woo (Department of Pharmacy, Korea University) ;
  • Jun, Woojin (Department of Food and Nutrition, Chonnam National University) ;
  • Yoon, Suk Ran (Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee, Sang-Chul (Research Center for Integrative Cellulomics, Korea Research Institute of Bioscience and Biotechnology) ;
  • Chung, Jin Woong (Department of Biological Science, Dong-A University)
  • Received : 2014.02.05
  • Accepted : 2014.03.13
  • Published : 2014.06.28

Abstract

In this study, we performed two-dimensional electrophoresis with protein extracts from lizard tails, and analyzed the protein expression profiles during the tissue regeneration to identify the dedifferentiation factor. As a result, we identified 18 protein spots among total of 292 spots, of which proteins were specifically expressed during blastema formation. We selected lactoferrin as a candidate because it is the mammalian homolog of leech-derived tryptase inhibitor, which showed the highest frequency among the 18 proteins. Lactoferrin was specifically expressed in various stem cell lines, and enhanced the efficiency of iPSC generation upto approximately 7-fold relative to the control. Furthermore, lactoferrin increased the efficiency by 2-fold without enforced expression of Klf4. These results suggest that lactoferrin may induce dedifferentiation, at least partly by increasing the expression of Klf4.

Keywords

References

  1. Alibardi L. 2010. Morphological and cellular aspects of tail and limb regeneration in lizards. A model system with implications for tissue regeneration in mammals. Adv. Anat. Embryol. Cell Biol. 207: 1-109. https://doi.org/10.1007/978-3-642-03733-7_1
  2. Baranowitz SA, Maderson PF, Connelly TG. 1979. Lizard and newt tail regeneration: a quantitative study. J. Exp. Zool. 210: 17-37. https://doi.org/10.1002/jez.1402100104
  3. Bayart E, Cohen-Haguenauer O. 2013. Technological overview of iPS induction from human adult somatic cells. Curr. Gene Ther. 13: 73-92. https://doi.org/10.2174/1566523211313020002
  4. Delorme SL, Lungu IM, Vickaryous MK. 2012. Scar-free wound healing and regeneration following tail loss in the leopard gecko, Eublepharis macularius. Anat. Rec. (Hoboken) 295: 1575-1595. https://doi.org/10.1002/ar.22490
  5. Di Marco S, Priestle JP. 1997. Structure of the complex of leech-derived tryptase inhibitor (LDTI) with trypsin and modeling of the LDTI-tryptase system. Structure 5: 1465-1474. https://doi.org/10.1016/S0969-2126(97)00296-7
  6. Elrod KC, Moore QR, Abraham WM, Tanaka RD. 1997. Lactoferrin, a potent tryptase inhibitor, abolishes late-phase airway responses in allergic sheep. Am. J. Respir. Crit. Care Med. 156: 375-381. https://doi.org/10.1164/ajrccm.156.2.9607012
  7. Franco C, Soares R, Pires E, Koci K, Almeida AM, Santos R, Coelho AV. 2013. Understanding regeneration through proteomics. Proteomics 13: 686-709. https://doi.org/10.1002/pmic.201200397
  8. Gan X, Liu D, Huang P, Gao W, Chen X, Hei Z. 2012. Mastcell- releasing tryptase triggers acute lung injury induced by small intestinal ischemia-reperfusion by activating PAR-2 in rats. Inflammation 35: 1144-1153. https://doi.org/10.1007/s10753-011-9422-5
  9. Grotek B, Wehner D, Weidinger G. 2013. Notch signaling coordinates cellular proliferation with differentiation during zebrafish fin regeneration. Development 140: 1412-1423. https://doi.org/10.1242/dev.087452
  10. Hernandez-Hernandez L, Sanz C, García-Solaesa V, Padrón J, García-Sánchez A, Dávila I, et al. 2012. Tryptase: genetic and functional considerations. Allergol. Immunopathol. (Madr) 40: 385-389. https://doi.org/10.1016/j.aller.2012.04.004
  11. Huangfu D, Osafune K, Maehr R, Guo W, Eijkelenboom A, Chen S, et al. 2008. Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat. Biotechnol. 26: 1269-1275. https://doi.org/10.1038/nbt.1502
  12. Kaneko S, Yamanaka S. 2013. To be immunogenic, or not to be: that's the iPSC question. Cell Stem Cell 12: 385-386. https://doi.org/10.1016/j.stem.2013.03.008
  13. K im MJ, Son MJ, Son MY, Seol B, K im J , Park J, et al. 2011. Generation of human induced pluripotent stem cells from osteoarthritis patient-derived synovial cells. Arthritis Rheum. 63: 3010-3021. https://doi.org/10.1002/art.30488
  14. Kruzel ML, Bacsi A, Choudhury B, Sur S, Boldogh I. 2006. Lactoferrin decreases pollen antigen-induced allergic airway inflammation in a murine model of asthma. Immunology 119: 159-166. https://doi.org/10.1111/j.1365-2567.2006.02417.x
  15. McLean KE, Vickaryous MK. 2011. A novel amniote model of epimorphic regeneration: the leopard gecko, Eublepharis macularius. BMC Dev. Biol. 11: 50. https://doi.org/10.1186/1471-213X-11-50
  16. Nakagawa M, Kyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, et al. 2008. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat. Biotechnol. 26: 101-106. https://doi.org/10.1038/nbt1374
  17. Pietronave S, Prat M. 2012. Advances and applications of induced pluripotent stem cells. Can. J. Physiol. Pharmacol. 90: 317-325. https://doi.org/10.1139/y11-125
  18. Rink JC. 2013. Stem cell systems and regeneration in planaria. Dev. Genes Evol. 223: 67-84. https://doi.org/10.1007/s00427-012-0426-4
  19. Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K. 2008. Induced pluripotent stem cells generated without viral integration. Science 322: 945-949. https://doi.org/10.1126/science.1162494
  20. Takahashi K, Yamanaka S. 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126: 663-676. https://doi.org/10.1016/j.cell.2006.07.024
  21. Takahashi K, Okita K, Nakagawa M, Yamanaka S. 2007. Induction of pluripotent stem cells from fibroblast cultures. Nat. Protoc. 2: 3081-3089. https://doi.org/10.1038/nprot.2007.418
  22. Takayama Y, Aoki R. 2012. Roles of lactoferrin on skin wound healing. Biochem. Cell Biol. 90: 497-503. https://doi.org/10.1139/o11-054
  23. Tamura K, Ohgo S, Yokoyama H. 2010. Limb blastema cell: a stem cell for morphological regeneration. Dev. Growth Differ. 52: 89-99.
  24. Tang L, Wu JJ, Ma Q, Cui T, Andreopoulos FM, Gil J, et al. 2010. Human lactoferrin stimulates skin keratinocyte function and wound re-epithelialization. Br. J. Dermatol. 163: 38-47.
  25. Tang L, Cui T, Wu JJ, Liu-Mares W, Huang N, Li J. 2010. A rice-derived recombinant human lactoferrin stimulates fibroblast proliferation, migration, and sustains cell survival. Wound Repair Regen. 18: 123-131. https://doi.org/10.1111/j.1524-475X.2009.00563.x
  26. Wernig M, Meissner A, Cassady JP, Jaenisch R. 2008. c-Myc is dispensable for direct reprogramming of mouse fibroblasts. Cell Stem Cell 2: 10-12. https://doi.org/10.1016/j.stem.2007.12.001
  27. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, et al. 2007. Induced pluripotent stem cell lines derived from human somatic cells. Science 318: 1917-1920. https://doi.org/10.1126/science.1151526

Cited by

  1. Spot the difference: Solving the puzzle of hidden pictures in the lizard genome for identification of regeneration factors vol.49, pp.5, 2014, https://doi.org/10.5483/bmbrep.2016.49.5.045
  2. Review: The Regenerating Tail Blastema of Lizards as a Model to Study Organ Regeneration and Tumor Growth Regulation in Amniotes vol.302, pp.9, 2014, https://doi.org/10.1002/ar.24029