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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Keratinocytes


High impact information on Keratinocytes

  • Notch1 deficiency in skin and in primary keratinocytes results in increased and sustained expression of Gli2, causing the development of basal-cell carcinoma-like tumors [6].
  • CDSN, a glycoprotein expressed in the epidermis and inner root sheath (IRS) of hair follicles, is a keratinocyte adhesion molecule [7].
  • Adult K14.MYC2 mice gradually lose their hair and develop spontaneous ulcerated lesions due to a severe impairment in wound healing; their keratinocytes show impaired migration in response to wounding [8].
  • These differences were not dependent upon intercellular adhesion and were in marked contrast to keratinocytes conditionally null for another essential intercellular adhesion protein, desmoplakin (DP) [9].
  • Regulation of cytoplasmic calcium is impaired in cultured keratinocytes from HHD patients, and the normal epidermal calcium gradient is attenuated in vivo in HHD patients [10].

Chemical compound and disease context of Keratinocytes


Biological context of Keratinocytes

  • Specifically, the maternal allele surrounding the mutation site on COL17A1 (1706delA) showed reversion of the mutation and loss of heterozygosity along a tract of at least 381 bp in revertant keratinocytes derived from clinically unaffected skin patches; the paternal mutation (R1226X) remained present in all cell samples [16].
  • In the patients with epidermal nevi, point mutations in 50 percent of the K10 alleles of epidermal cells were found in keratinocytes from lesional skin; no mutations were detected in normal skin [17].
  • Here we report that when fibronectin is added to the methylcellulose, keratinocytes still withdraw from the cell cycle, but induction of involucrin expression is largely inhibited [18].
  • Our results suggest that the critical function of IKK2-mediated NF-kappa B activity in epidermal keratinocytes is to regulate mechanisms that maintain the immune homeostasis of the skin [19].
  • The function of keratinocyte growth factor (KGF) in normal and wounded skin was assessed by expression of a dominant-negative KGF receptor transgene in basal keratinocytes [20].

Anatomical context of Keratinocytes


Associations of Keratinocytes with chemical compounds


Gene context of Keratinocytes

  • Here we show that CD44-dependent GAS binding to polarized monolayers of human keratinocytes induced marked cytoskeletal rearrangements manifested by membrane ruffling and disruption of intercellular junctions [28].
  • Epidermal basal keratinocytes produced CCL27 protein that bound to extracellular matrix, mediated adhesion and was displayed on the surface of dermal endothelial cells [29].
  • We used retroviral transduction of normal human keratinocytes to constitutively express SHH [30].
  • IKK2 deficiency inhibits NF-kappa B activation, but does not lead to cell-autonomous hyperproliferation or impaired differentiation of keratinocytes [19].
  • SHH-expressing cells demonstrated increased expression of both the known HH target, BMP-2B, as well as bcl-2, a protein prominently expressed by keratinocytes in BCCs [30].

Analytical, diagnostic and therapeutic context of Keratinocytes


  1. TGF-beta 1 inhibition of c-myc transcription and growth in keratinocytes is abrogated by viral transforming proteins with pRB binding domains. Pietenpol, J.A., Stein, R.W., Moran, E., Yaciuk, P., Schlegel, R., Lyons, R.M., Pittelkow, M.R., Münger, K., Howley, P.M., Moses, H.L. Cell (1990) [Pubmed]
  2. MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Coussens, L.M., Tinkle, C.L., Hanahan, D., Werb, Z. Cell (2000) [Pubmed]
  3. Herlitz's junctional epidermolysis bullosa is linked to mutations in the gene (LAMC2) for the gamma 2 subunit of nicein/kalinin (LAMININ-5). Aberdam, D., Galliano, M.F., Vailly, J., Pulkkinen, L., Bonifas, J., Christiano, A.M., Tryggvason, K., Uitto, J., Epstein, E.H., Ortonne, J.P. Nat. Genet. (1994) [Pubmed]
  4. Altered metabolism of mast-cell growth factor (c-kit ligand) in cutaneous mastocytosis. Longley, B.J., Morganroth, G.S., Tyrrell, L., Ding, T.G., Anderson, D.M., Williams, D.E., Halaban, R. N. Engl. J. Med. (1993) [Pubmed]
  5. Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model. Sano, S., Chan, K.S., Carbajal, S., Clifford, J., Peavey, M., Kiguchi, K., Itami, S., Nickoloff, B.J., DiGiovanni, J. Nat. Med. (2005) [Pubmed]
  6. Notch1 functions as a tumor suppressor in mouse skin. Nicolas, M., Wolfer, A., Raj, K., Kummer, J.A., Mill, P., van Noort, M., Hui, C.C., Clevers, H., Dotto, G.P., Radtke, F. Nat. Genet. (2003) [Pubmed]
  7. Hypotrichosis simplex of the scalp is associated with nonsense mutations in CDSN encoding corneodesmosin. Levy-Nissenbaum, E., Betz, R.C., Frydman, M., Simon, M., Lahat, H., Bakhan, T., Goldman, B., Bygum, A., Pierick, M., Hillmer, A.M., Jonca, N., Toribio, J., Kruse, R., Dewald, G., Cichon, S., Kubisch, C., Guerrin, M., Serre, G., Nöthen, M.M., Pras, E. Nat. Genet. (2003) [Pubmed]
  8. Deregulated expression of c-Myc depletes epidermal stem cells. Waikel, R.L., Kawachi, Y., Waikel, P.A., Wang, X.J., Roop, D.R. Nat. Genet. (2001) [Pubmed]
  9. Hyperproliferation and defects in epithelial polarity upon conditional ablation of alpha-catenin in skin. Vasioukhin, V., Bauer, C., Degenstein, L., Wise, B., Fuchs, E. Cell (2001) [Pubmed]
  10. Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease. Hu, Z., Bonifas, J.M., Beech, J., Bench, G., Shigihara, T., Ogawa, H., Ikeda, S., Mauro, T., Epstein, E.H. Nat. Genet. (2000) [Pubmed]
  11. Pemphigus antibodies identify a cell surface glycoprotein synthesized by human and mouse keratinocytes. Stanley, J.R., Yaar, M., Hawley-Nelson, P., Katz, S.I. J. Clin. Invest. (1982) [Pubmed]
  12. Polycyclic aromatic hydrocarbon mutagenesis of human epidermal keratinocytes in culture. Allen-Hoffmann, B.L., Rheinwald, J.G. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  13. 1,25-Dihydroxyvitamin D3 enhances the expression of transforming growth factor beta 1 and its latent form binding protein in cultured breast carcinoma cells. Koli, K., Keski-Oja, J. Cancer Res. (1995) [Pubmed]
  14. Protein kinase Cdelta-mediated phosphorylation of alpha6beta4 is associated with reduced integrin localization to the hemidesmosome and decreased keratinocyte attachment. Alt, A., Ohba, M., Li, L., Gartsbein, M., Belanger, A., Denning, M.F., Kuroki, T., Yuspa, S.H., Tennenbaum, T. Cancer Res. (2001) [Pubmed]
  15. Randomized phase I trial of recombinant human keratinocyte growth factor plus chemotherapy: potential role as mucosal protectant. Meropol, N.J., Somer, R.A., Gutheil, J., Pelley, R.J., Modiano, M.R., Rowinsky, E.K., Rothenberg, M.L., Redding, S.W., Serdar, C.M., Yao, B., Heard, R., Rosen, L.S. J. Clin. Oncol. (2003) [Pubmed]
  16. Revertant mosaicism in epidermolysis bullosa caused by mitotic gene conversion. Jonkman, M.F., Scheffer, H., Stulp, R., Pas, H.H., Nijenhuis, M., Heeres, K., Owaribe, K., Pulkkinen, L., Uitto, J. Cell (1997) [Pubmed]
  17. Genetic and clinical mosaicism in a type of epidermal nevus. Paller, A.S., Syder, A.J., Chan, Y.M., Yu, Q.C., Hutton, E., Tadini, G., Fuchs, E. N. Engl. J. Med. (1994) [Pubmed]
  18. Fibronectin inhibits the terminal differentiation of human keratinocytes. Adams, J.C., Watt, F.M. Nature (1989) [Pubmed]
  19. TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2. Pasparakis, M., Courtois, G., Hafner, M., Schmidt-Supprian, M., Nenci, A., Toksoy, A., Krampert, M., Goebeler, M., Gillitzer, R., Israel, A., Krieg, T., Rajewsky, K., Haase, I. Nature (2002) [Pubmed]
  20. The function of KGF in morphogenesis of epithelium and reepithelialization of wounds. Werner, S., Smola, H., Liao, X., Longaker, M.T., Krieg, T., Hofschneider, P.H., Williams, L.T. Science (1994) [Pubmed]
  21. Enzymatic cross-linking of involucrin and other proteins by keratinocyte particulates in vitro. Simon, M., Green, H. Cell (1985) [Pubmed]
  22. Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression. Jones, P.H., Watt, F.M. Cell (1993) [Pubmed]
  23. Regulation of terminal differentiation of cultured human keratinocytes by vitamin A. Fuchs, E., Green, H. Cell (1981) [Pubmed]
  24. Telomerase activation by the E6 gene product of human papillomavirus type 16. Klingelhutz, A.J., Foster, S.A., McDougall, J.K. Nature (1996) [Pubmed]
  25. Changes in keratinocyte adhesion during terminal differentiation: reduction in fibronectin binding precedes alpha 5 beta 1 integrin loss from the cell surface. Adams, J.C., Watt, F.M. Cell (1990) [Pubmed]
  26. Cyclic AMP in relation to proliferation of the epidermal cell: a new view. Green, H. Cell (1978) [Pubmed]
  27. Sulfonation and molecular action. Strott, C.A. Endocr. Rev. (2002) [Pubmed]
  28. Group A Streptococcus tissue invasion by CD44-mediated cell signalling. Cywes, C., Wessels, M.R. Nature (2001) [Pubmed]
  29. CCL27-CCR10 interactions regulate T cell-mediated skin inflammation. Homey, B., Alenius, H., Müller, A., Soto, H., Bowman, E.P., Yuan, W., McEvoy, L., Lauerma, A.I., Assmann, T., Bünemann, E., Lehto, M., Wolff, H., Yen, D., Marxhausen, H., To, W., Sedgwick, J., Ruzicka, T., Lehmann, P., Zlotnik, A. Nat. Med. (2002) [Pubmed]
  30. Induction of basal cell carcinoma features in transgenic human skin expressing Sonic Hedgehog. Fan, H., Oro, A.E., Scott, M.P., Khavari, P.A. Nat. Med. (1997) [Pubmed]
  31. An endocrine approach to the control of epidermal growth: serum-free cultivation of human keratinocytes. Maciag, T., Nemore, R.E., Weinstein, R., Gilchrest, B.A. Science (1981) [Pubmed]
  32. Epithelial wound healing enhanced by transforming growth factor-alpha and vaccinia growth factor. Schultz, G.S., White, M., Mitchell, R., Brown, G., Lynch, J., Twardzik, D.R., Todaro, G.J. Science (1987) [Pubmed]
  33. Loss of plectin causes epidermolysis bullosa with muscular dystrophy: cDNA cloning and genomic organization. McLean, W.H., Pulkkinen, L., Smith, F.J., Rugg, E.L., Lane, E.B., Bullrich, F., Burgeson, R.E., Amano, S., Hudson, D.L., Owaribe, K., McGrath, J.A., McMillan, J.R., Eady, R.A., Leigh, I.M., Christiano, A.M., Uitto, J. Genes Dev. (1996) [Pubmed]
  34. Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing. Brown, L.F., Yeo, K.T., Berse, B., Yeo, T.K., Senger, D.R., Dvorak, H.F., van de Water, L. J. Exp. Med. (1992) [Pubmed]
  35. Interleukin-1 receptor antagonist in normal and psoriatic epidermis. Hammerberg, C., Arend, W.P., Fisher, G.J., Chan, L.S., Berger, A.E., Haskill, J.S., Voorhees, J.J., Cooper, K.D. J. Clin. Invest. (1992) [Pubmed]
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