Russian Journal of Developmental Biology

, Volume 36, Issue 2, pp 61–64 | Cite as

Apoptosis and differentiation of epidermal keratinocytes

  • V. V. Terskikh
  • A. V. Vasil’ev


We compared some processes characteristic for both apoptosis and terminal differentiation of epidermal keratinocytes. It can be proposed that nonapoptotic programmed cell death takes place during differentiation of keratinocytes. Apoptosis and terminal differentiation of keratinocytes appear to be different events but some similar molecular mechanisms are involved in both processes.

Key words

keratinocytes apoptosis differentiation 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adams, J.C. and Watt, F.M., Fibronectin Inhibits the Terminal Differentiation of Human Keratinocytes, Nature, 1989, vol. 340, pp. 307–309.CrossRefPubMedGoogle Scholar
  2. Adams, J.C. and Watt, F.M., Changes in Keratinocytes Adhesion during Terminal Differentiation: Reduction in Fibronectin Binding Precedes alpha-5-beta-1 Integrin Loss from the Cell Surface, Cell, 1990, vol. 63, pp. 425–435.CrossRefPubMedGoogle Scholar
  3. Bates, R.C., Buret, A., van Helden, D.F., et al., Apoptosis Induced by Inhibition of Intercellular Contact, J. Cell Biol., 1994, vol. 125, pp. 403–415.CrossRefPubMedGoogle Scholar
  4. Bernerd, F. and Asselineau, D., Successive Alteration and Recovery of Epidermal Differentiation and Morphogenesis after Specific UVB-Damages in Skin Reconstructed in vitro, Devel. Biol., 1997, vol. 183, pp. 123–138.CrossRefGoogle Scholar
  5. Boudreau, N., Sympson, C., Werb, Z., and Bissell, M.J., Suppression of ICE and Apoptosis in Mammary Epithelial Cells by Extracellular Matrix, Science, 1995, vol. 267, pp. 891–893.PubMedGoogle Scholar
  6. Boudreau, N., Werb, Z., and Bissel, M.J., Suppression of Apoptosis by Basement Membrane Requires Three-Dimensional Tissue Organization and Withdrawal from the Cell Cycle, Proc. Natl. Acad. Sci. USA, 1996, vol. 93, pp. 3509–3513.CrossRefPubMedGoogle Scholar
  7. Brachmann, R., Lindquist, P.B., Nagashima, M., et al., Transmembrane TGF-α Precursors Activate EGF/TGF-α Receptor, Cell, 1989, vol. 56, pp. 691–700.CrossRefPubMedGoogle Scholar
  8. Coffey, R.J., Derynck, R., Wilcox, J.N., et al., Production and Autoinduction of Transforming Growth Factor-α in Human Keratinocytes, Nature, 1987, vol. 328, pp. 817–820.CrossRefPubMedGoogle Scholar
  9. Chaturvedi, V., Qin, J.-Z., Denning, M.F., et al., Apoptosis in Proliferating, Senescent, and Immortalized Keratinocytes, J. Biol. Chem., 1999, vol. 274, pp. 23 358–23 367.Google Scholar
  10. Chylicki, K., Ehinger, M., Svedberg, H., and Gullberg, U., Characterization of the Molecular Mechanisms for P53-Mediated Differentiation, Cell Death Differ., 2000, vol. 11, pp. 561–571.Google Scholar
  11. Collins, M.K.L., Perkins, G.R., Rodriguez-Tarduchy, G., et al., Growth Factors as Survival Factors: Regulation of Apoptosis, BioEssays, 1994, vol. 16, pp. 133–138.CrossRefPubMedGoogle Scholar
  12. Fesus, L., Madi, A., Balajthy, Z., et al., Transglutaminase Induction by Various Cell Death and Apoptosis Pathways, Experientia, 1996, vol. 52, pp. 942–949.PubMedGoogle Scholar
  13. Frisch, S.M. and Francis, H., Disruption of Epithelial Cell-Matrix Interactions Induces Apoptosis, J. Cell Biol., 1994, vol. 124, pp. 619–626.CrossRefPubMedGoogle Scholar
  14. Fuchs, E. and Cleveland, D.W., A Structural Scaffolding of Intermediate Filaments in Health and Disease, Science, 1998, vol. 279, pp. 514–519.CrossRefPubMedGoogle Scholar
  15. Gandarillas, A. and Watt, F.M., c-Myc Promotes Differentiation of Human Epidermal Cells, Genes Devel., 1997, vol. 11, pp. 2869–2882.PubMedGoogle Scholar
  16. Gandarillas, A., Goldsmith, L.A., Gschmeisner, S., et al., Evidence That Apoptosis and Terminal Differentiation of Epidermal Keratinocytes Are Distinct Processes, Exp. Dermatol., 1999, vol. 8, pp. 71–79.PubMedGoogle Scholar
  17. Giancotti, F.G., Integrin Signaling: Specificity and Control of Cell Survival and Cell Cycle Progression, Curr. Opin. Cell Biol., 1997, vol. 9, pp. 691–700.CrossRefPubMedGoogle Scholar
  18. Green, H., Terminal Differentiation of Cultured Human Epidermal Cells, Cell, 1977, vol. 11, pp. 405–416.CrossRefPubMedGoogle Scholar
  19. Griffin, M., Casadio, R., and Bergamini, C.M., Transglutaminases: Nature’s Biological Glues, Biochem. J., 2002, vol. 368, pp. 377–396.CrossRefPubMedGoogle Scholar
  20. Gunn, J., Bodner, J.B., Knowles, S.E., and Ballard, F.J., Inhibition of Protein Breakdown by Epidermal Growth Factor in JMR90 Human Fibroblasts and Other Mammalian Cell Lines, Biochem. J., 1983, vol. 210, pp. 251–258.PubMedGoogle Scholar
  21. Haake, A.R. and Cookis, M., Incomplete Differentiation of Fetal Keratinocytes in the Skin Equivalent Leads to the Default Pathway of Apoptosis, Exp. Cell Res., 1997, vol. 231, pp. 83–95.CrossRefPubMedGoogle Scholar
  22. Haake, A.R. and Polakowska, R.R., Cell Death by Apoptosis in Epidermal Biology, J. Invest. Dermatol., 1993, vol. 101, pp. 107–112.CrossRefPubMedGoogle Scholar
  23. Hall, P.A., Coates, P.J., Ansari, B., and Hopwood, D., Cell Deat in Embryogenesis, Cell Death in Biology and Pathology, Lockshin, R.A. and Bowen, I.D., Eds., New York: Chapman and Hall, 1981, pp. 35–78.Google Scholar
  24. Hall, P.A., Coates, P.J., Ansari, B., and Hopwood, D., Regulation of Cell Number in the Mammalian Gastrointestinal Tract: The Importance of Apoptosis, J. Cell Sci., 1994, vol. 107, pp. 3569–3577.PubMedGoogle Scholar
  25. Jacobson, M.D., Weil, M., and Raff, M.C., Programmed Cell Death in Animal Development, Cell, 1997, vol. 88, pp. 347–354.CrossRefPubMedGoogle Scholar
  26. Juin, P., Hueber, A.O., Littlewood, T., and Evan, G., c-Myc-Induced Sensitization to Apoptosis Is Mediated through Cytochrome c Release, Genes Devel., 1999, vol. 13, pp. 1367–1381.PubMedGoogle Scholar
  27. Liao, W.-T., Chang, K.L., Yu, C.-L., et al., Arsenic Induces Human Keratinocyte Apoptosis by the FAS/FAS Ligand Pathway, which Correlates with Alternations in Nuclear Factor-KB and Activator Protein-1 Activity, J. Invest. Dermatol., 2004, vol. 122, pp. 125–129.CrossRefPubMedGoogle Scholar
  28. Lu, Q.L., Poulsom, R., Wong, L., and Hanby, A.V., Bcl-2 Expression in Adult and Embryonic Non-Haematopoietic Tissues, J. Pathol., 1993, vol. 169, pp. 431–437.PubMedGoogle Scholar
  29. Majno, G. and Joris, I., Apoptosis, Oncosis, and Necrosis. An Overview of Cell Death, Am. J. Pathol., 1995, vol. 146, pp. 3–15.PubMedGoogle Scholar
  30. Maruoka, Y., Harada, H., Mitsuyasu, T., et al., Keratinocytes Become Terminally Differentiated in a Process Involving Programmed Cell Death, Biochem. Biophys. Res. Commun., 1997, vol. 238, pp. 886–890.CrossRefPubMedGoogle Scholar
  31. McCall, C.A. and Cohen, J.J., Programmed Cell Death in Terminally Differentiating Keratinocytes: Role of Endogenous Endonuclease, J. Invest. Dermatol., 1991, vol. 97, pp. 111–115.CrossRefPubMedGoogle Scholar
  32. Meredith, J.E. and Schwartz, M.A., The Extracellular Matrix as a Cell Survival Factor, Mol. Biol. Cell, 1993, vol. 4, pp. 953–961.PubMedGoogle Scholar
  33. Meredith, J.E. and Schwartz, M.A., Integrins, Adhesion and Apoptosis, Trends Cell Biol., 1997, vol. 7, pp. 146–150.CrossRefGoogle Scholar
  34. Metcalfe, A. and Streuli, C., Epithelial Apoptosis, BioEssays, 1997, vol. 19, pp. 711–720.CrossRefPubMedGoogle Scholar
  35. Miettinen, P.J., Berger, J.E., Meneses, J., et al., Epithelial Immaturity and Multiorgan Failure in Mice Lacking Epidermal Growth Factor Receptor, Nature, 1995, vol. 376, pp. 337–341.CrossRefPubMedGoogle Scholar
  36. Moro, L., Venturino, M., Bozzo, C., et al., Integrins Induce Activation of EGF Receptor: Role in MAP Kinase Induction and Adhesion-Dependent Cell Survival, EMBO J., 1998, vol. 17, pp. 6622–6632.CrossRefPubMedGoogle Scholar
  37. Nicholson, L.J. and Watt, F.M., Decreased Expression of Fibronectin and the α5β1 Integrin during Terminal Differentiation of Human Keratinocytes, J. Cell Sci., 1991, vol. 98, pp. 225–232.PubMedGoogle Scholar
  38. Nagata, S., Apoptosis by Death Factor, Cell, 1997, vol. 88, pp. 355–365.CrossRefPubMedGoogle Scholar
  39. O’Keefe, E., Battin, T., and Payne, R.I., Epidermal Growth Factor Receptor in Human Epithelial Cells: Direct Demonstration in Cultured Cells, J. Cell Sci., 1982, vol. 78, pp. 482–488.Google Scholar
  40. Packham, G. and Cleaveland, J.L., c-Myc and Apoptosis, Biochem. Biophys. Acta, 1995, vol. 1242, pp. 11–28.PubMedGoogle Scholar
  41. Papp, H., Czifra, G., Bodo, E., et al., Opposite Roles of Protein Kinase C Isoforms in Proliferation, Differentiation, Apoptosis, and Tumorigenicity of Human HaCaT Keratinocytes, Cell. Mol. Life Sci., 2004, vol. 61, pp. 1095–1105.CrossRefPubMedGoogle Scholar
  42. Partridge, M., Green, M.R., Langdon, I.D., and Feldman, M., Production of TGF-α and TGF-β by Cultured Keratinocytes, Skin and Oral Squamous Cell Carcinomas—Potential Autocrine Regulation of Normal and Malignant Epithelial Cell Proliferation, Brit. J. Cancer, 1989, vol. 60, pp. 542–548.PubMedGoogle Scholar
  43. Pena, J.C., Fuchs, E., and Thompson, C.B., Bcl-x Expression Influences Keratinocyte Cell Survival but not Terminal Differentiation, Cell Growth Differ., 1997, vol. 8, pp. 619–629.PubMedGoogle Scholar
  44. Polakowska, R.R., Piacentini, M., Barlett, R., et al., Apoptosis in Human Skin Development: Morphogenesis, Periderm, and Stem Cells, Devel. Dyn., 1994, vol. 199, pp. 176–188.Google Scholar
  45. Raff, M., Social Controls on Cell Survival and Cell Death, Nature, 1992, vol. 356, pp. 397–400.CrossRefPubMedGoogle Scholar
  46. Rawson, C.L., Loo, D.T., Duimstra, J.R., et al., Death of Serum-Free Mouse Embryo Cells Caused by Epidermal Growth Factor Deprivation, J. Cell Biol., 1991, vol. 113, pp. 671–680.CrossRefPubMedGoogle Scholar
  47. Reginato, M.J., Mills, K.R., Paulus, J.K., et al., Integrins and EFGR Coordinately Regulate the Pro-Apoptotic Protein Bim to Prevent Anoikis, Nature Cell Biol., 2003, vol. 5, pp. 733–740.CrossRefPubMedGoogle Scholar
  48. Rice, R.H., Mehrpouyan, M., Qin, Q., and Phillips, M.A., Transglutaminases in Keratinocytes, The Keratinocyte Handbook, Cambridge: Cambridge Univ. Press, 1994, pp. 259–274.Google Scholar
  49. Ruoslahti, E. and Reed, J., Anchorage, Independence, Integrins and Apoptosis, Cell, 1994, vol. 77, pp. 477–478.CrossRefPubMedGoogle Scholar
  50. Salvesen, G.S. and Dixit, V.M., Caspases: Intracellular Signaling by Proteolysis, Cell, 1997, vol. 91, pp. 443–446.PubMedGoogle Scholar
  51. Soma, T., Ogo, M., Suzuki, J., et al., Analysis of Apoptotic Cell Death in Human Hair Follicles in vivo and in vitro, J. Invest. Dermatol., 1998, vol. 111, pp. 948–954.CrossRefPubMedGoogle Scholar
  52. Sperandio, S., De Belle, I., and Bredesen, D.E., An Alternative, Nonapoptotic Form of Programmed Cell Death, Proc. Natl. Acad. Sci. USA, 2000, vol. 97, pp. 14376–14381.CrossRefPubMedGoogle Scholar
  53. Strange, R., Li, F., Saurer, S., et al., Apoptotic Cell Death and Tissue Remodelling during Mouse Mammary Gland Involution, Development, 1992, vol. 115, pp. 49–58.PubMedGoogle Scholar
  54. Su, H.Y., Cheng, W.T., Chen, S.C., et al., Mouse Keratinocytes Express c98 Gene Homologous to bcl-2, That Is Stimulated by Insulin-Like Growth Factor 1 and Prevents Dexamethasone-Induced Apoptosis, Biochem. Biophys. Acta, 2004, vol. 1676, pp. 127–137.PubMedGoogle Scholar
  55. Takahashi, T., Ogo, M., and Hibino, T., Partial Purification and Characterization of Two Distinct Types of Caspases from Human Epidermis, J. Invest. Dermatol., 1998, vol. 111, pp. 367–372.CrossRefPubMedGoogle Scholar
  56. Tamm, I. and Kikuchi, T., Activation of Signal Transduction Pathways Protect Quiescent Balb/c-3T3 Fibroblasts against Death due to Serum Deprivation, J. Cell. Physiol., 1991, vol. 148, no.1, pp. 85–95.CrossRefPubMedGoogle Scholar
  57. Vaux, D.L. and Korsmeyer, S.J., Cell Death in Development, Cell, 1999, vol. 96, pp. 245–254.CrossRefPubMedGoogle Scholar
  58. Watt, F.M., Kubler, M.-D., Hotchin, N.A., et al., Regulation of Keratinocyte Terminal Differentiation by Integrin-Extracellular Matrix Interactions, J. Cell Sci., 1993, vol. 106, pp. 175–182.PubMedGoogle Scholar
  59. White, E., Life, Death, and the Pursuit of Apoptosis, Genes Devel., 1996, vol. 10, pp. 1–15.PubMedGoogle Scholar
  60. Wyllie, A.H., Kerr, J.F.R., and Currie, A.R., Cell Death: The Significance of Apoptosis, Int. Rev. Cytol., 1980, vol. 68, pp. 251–270.PubMedGoogle Scholar

Copyright information

© MAIK “Nauka/Interperiodica” 2005

Authors and Affiliations

  • V. V. Terskikh
    • 1
  • A. V. Vasil’ev
    • 1
  1. 1.Kol’tsov Institute of Developmental BiologyRussian Academy of SciencesMoscowRussia

Personalised recommendations