2012, Number 5
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ABSTRACTBackground: mammals have limited epithelial regeneration capacity. The K6b-E6/E7 mice model has been described as useful for the study of epithelial regeneration. The objective of this study is to compare the expression of E6/E7 oncogenes with those of cell proliferation and apoptosis during epithelization. The hypothesis of this study is that alterations in cell proliferation and apoptosis in K6b-E6/E7 mice will only occur during epithelization.
Methods: deep 2 mm punches were performed in the middle of transgenic and control mice’s ears. A biopsy was collected from the epithelization zone 72-hours and 2-weeks post-injury. Assays for cell proliferation and apoptosis were carried out by immunohistochemistry and TUNEL techniques, respectively. RT-PCR in situ was performed to compare E6/E7 expressions in the areas studied.
Results: transgenic strain K6b-E6/E7 presented more proliferative cells and less apoptotic cells in epithelizated zones. This effect was limited to suprabasal stratum only, and correlates with E6/E7 oncogenes expression. Two weeks post-injure, cell proliferation and apoptosis were similar in both samples as the E6/E7 expression went down.
Conclusion: K6b-E6/E7 mouse model is useful for epithelial regeneration. Its mechanisms should be considered for the treatment of deep wounds.
Brockes JP, Kumar A. Plasticity and reprogramming of differentiated cells in amphibian regeneration. Nat Rev Mol Cell Biol 2002;3:566-574.
Morrison JI, Lööf S, He P, Simon A. Salamander limb regeneration involves the activation of a multipotent skeletal muscle satellite cell population. J Cell Biol 2006;172(3):433-440.
Carlson BM. Some principles of regeneration in mammalian systems. Anat Rec B New Anat 2005;287B(1):4-13.
Martin P. Wound Healing-Aiming for Perfect Skin Regeneration. Science 1997;76(4):75-81.
Santoro MM, Gaudino G. Cellular and molecular facets of keratinocyte reepithelization during wound healing. Exp Cell Res 2005;304(1):274-286.
Echeverri K, Tanaka EM. Ectoderm to Mesoderm Lineage Switching During Axolotl Tail Regeneration. Science 2002;298(5600):1993-1996.
Goss RJ, Grimes LN. Epidermal downgrowths in regenerating rabbit ear holes. J Morphol 1975;146(4):533-542.
Clark LD, Clark RK, Heber-Katz E. A New Murine Model for Mammalian Wound Repair and Regeneration. Clin Immunol Immunopathol 1998;88(1):35-45.
Valencia C, Bonilla-Delgado J, Oktaba K, Ocádiz-Delgado R, Gariglio P, Covarrubias L. Human Papillomavirus E6/E7 Oncogenes Promote Mouse Ear Regeneration by Increasing the Rate of Wound Re-epithelization and Epidermal Growth. J Invest Dermatol 2008;128:2894-2903.
Escalante-Alcalde D, Recillas-Targa F, Valencia C, Santa-Olalla J, Chávez P, Marroquín A, et al. Expression of E6 and E7 papillomavirus oncogenes in the outer root sheath of hair follicles extends the growth phase and bypasses resting at telogen. Cell Growth Differ 2000;11(10):527-539.
Fuchs E. Scratching the surface of skin development. Nature 2007;445:834-842.
Navarro JM, Casatorres J, Jorcano JL. Elements Controlling the Expression and Induction of the Skin Hyperproliferation-associated Keratin K6. J Biol Chem 1995;270:21362-21367.
Tungteakkhun SS, Duerksen-Hughes PJ. Cellular binding partners of the human papillomavirus E6 protein. Arch Virol 2008;153(3):397- 408.
McLaughlin-Drubin ME, Münger K. The human papillomavirus E7 oncoprotein. Virology 2009;384(2):335-344.
Takahashi K, Paladini RD, Coulombe PA. Cloning and Characterization of Multiple Human Genes and cDNAs Encoding Highly Related Type II Keratin 6 Isoforms. J Biol Chem 1995;270:18581-18592.
Rothnagel JA, Seki T, Ogo M, Longley MA, Wojcik SM, Bundman DS, et al. The mouse keratin 6 isoforms are differentially expressed in the hair follicle, footpad, tongue and activated epidermis. Differentiation 1999;65(2):119-130.
Wazer DE, Liu XL, Chu Q, Gao Q, Band V. Immortalization of distinct human mammary epithelial cell types by human papilloma virus 16 E6 or E7. Proc Natl Acad Sci U S A 1995;92(9):3687-3691.
zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2002;2:342-350.
Song S, Pitot HC, Lambert PF. The Human Papillomavirus Type 16 E6 Gene Alone is Sufficient To Induce Carcinomas in Transgenic Animals. J Virol 1999;73(7):5887-5893.