Molecular and Cellular Biochemistry

, Volume 284, Issue 1–2, pp 183–188 | Cite as

Decreased keratinocyte motility in skin wound on mice lacking the epidermal fatty acid binding protein gene

  • Yoshiyuki Kusakari
  • Eisaku Ogawa
  • Yuji Owada
  • Noriko Kitanaka
  • Hiroshi Watanabe
  • Michiyo Kimura
  • Hachiro Tagami
  • Hisatake Kondo
  • Setsuya Aiba
  • Ryuhei OkuyamaEmail author


Fatty acids are shown to be important in various skin functions. Fatty acid binding protein (FABP) is postulated to serve as a lipid shuttle, solubilizing hydrophobic fatty acids and delivering them to the appropriate metabolic system. Among the FABP family proteins, epidermal-type FABP (E-FABP) is solely expressed in keratinocyte but its specific role in skin is not yet fully established. We found an elevated expression of E-FABP in regenerative keratinocytes of healing wounds. However, E-FABP null mice showed no marked differences compared to wild type mice in the process of wound closure, in vivo. On the other hand, in keratinocyte culture, E-FABP gene disruption decreased the cell motility, but did not affect the cell proliferation. E-FABP deletion may be compensated for in vivo by the microenvironment comprised of various cells such as fibroblasts and endothelial cells around the wound. Our analyses suggest that the E-FABP elevation may be necessary for the activation of cell motility within regenerative epidermis during wound healing.


cell motility FABP fatty acid keratinocyte regeneration wound healing 


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  1. 1.
    Coe NR, Bernlohr DA: Physiological properties and functions of intracellular fatty acid-binding proteins. Biochim Biophys Acta 1391: 287–306, 1998PubMedGoogle Scholar
  2. 2.
    Siegenthaler G, Hotz R, Chatellard-Gruaz D, Jaconi S, Saurat JH: Characterization and expression of a novel human fatty acid-binding protein: The epidermal type (E-FABP). Biochem Biophys Res Commun 190: 482–487, 1993PubMedCrossRefGoogle Scholar
  3. 3.
    Owada Y, Yoshimoto T, Kondo H: Spatio-temporally differential expression of genes for three members of fatty acid binding proteins in developing and mature rat brains. J Chem Neuroanat 12: 113–122, 1996PubMedCrossRefGoogle Scholar
  4. 4.
    O'Shaughnessy RF, Seery JP, Celis JE, Frischauf A, Watt FM: PA-FABP, a novel marker of human epidermal transit amplifying cells revealed by 2D protein gel electrophoresis and cDNA array hybridisation. FEBS Lett 486: 149–154, 2000PubMedCrossRefGoogle Scholar
  5. 5.
    Hansen HS, Jensen B: Essential function of linoleic acid esterified in acylglucosylceramide and acylceramide in maintaining the epidermal water permeability barrier. Evidence from feeding studies with oleate, linoleate, arachidonate, columbinate and alpha-linolenate. Biochim Biophys Acta 834: 357–363, 1985.Google Scholar
  6. 6.
    Lowe NJ, Stoughton RB: Essential fatty acid deficient hairless mouse: A model of chronic epidermal hyperproliferation. Br J Dermatol 96: 155–162, 1977PubMedCrossRefGoogle Scholar
  7. 7.
    Zamboni S, Zanetti G, Grosso G, Ambrosio GB, Gozzetti S, Peserico A: Dietary behaviour in psoriatic patients. Acta Derm Venereol Suppl (Stockh) 146: 182–183, 1989Google Scholar
  8. 8.
    Kragballe K, Fogh K: A low-fat diet supplemented with dietary fish oil (Max-EPA) results in improvement of psoriasis and in formation of leukotriene B5. Acta Derm Venereol 69: 23–28, 1989PubMedGoogle Scholar
  9. 9.
    Mayser P, Grimm H, Grimminger F: n−3 fatty acids in psoriasis. Br J Nutr 87(Suppl 1): S77–S82, 2002PubMedCrossRefGoogle Scholar
  10. 10.
    Jensen M, Groth L, Holmer G, Hansen HS, Fullerton A: The potential of the essential fatty acid-deficient hairless rat as a psoriasis screening model for topical anti-proliferative drugs. Skin Pharmacol Appl Skin Physiol 15: 401–413, 2002PubMedCrossRefGoogle Scholar
  11. 11.
    Zhu AJ, Haase I, Watt FM: Signaling via beta1 integrins and mitogen-activated protein kinase determines human epidermal stem cell fate in vitro. Proc Natl Acad Sci USA 96: 6728–6733, 1999PubMedCrossRefGoogle Scholar
  12. 12.
    Owada Y, Takano H, Yamanaka H, Kobayashi H, Sugitani Y, Tomioka Y, Suzuki I, Suzuki R, Terui T, Mizugaki M, Tagami H, Noda T, Kondo H: Altered water barrier function in epidermal-type fatty acid binding protein-deficient mice. J Invest Dermatol 118: 430–435, 2002PubMedCrossRefGoogle Scholar
  13. 13.
    Tan NS, Shaw NS, Vinckenbosch N, Liu P, Yasmin R, Desvergne B, Wahli W, Noy N: Selective cooperation between fatty acid binding proteins and peroxisome proliferator-activated receptors in regulating transcription. Mol Cell Biol 22: 5114–5127, 2002PubMedCrossRefGoogle Scholar
  14. 14.
    Mansbridge JN, Knapp AM: Changes in keratinocyte maturation during wound healing. J Invest Dermatol 89: 253–263, 1987PubMedCrossRefGoogle Scholar
  15. 15.
    Iizuka H, Ishida-Yamamoto A, Honda H: Epidermal remodelling in psoriasis. Br J Dermatol 135: 433–438, 1996PubMedCrossRefGoogle Scholar
  16. 16.
    Martin P: Wound healing-aiming for perfect skin regeneration. Science 276: 75–81, 1997PubMedCrossRefGoogle Scholar
  17. 17.
    Okuyama R, Nguyen BC, Talora C, Ogawa E, Tommasi di Vignano A, Lioumi M, Chiorino G, Tagami H, Woo M, Dotto GP: High commitment of embryonic keratinocytes to terminal differentiation through a Notch1-caspase 3 regulatory mechanism. Dev Cell 6: 551–562, 2004.Google Scholar
  18. 18.
    Roop D: Defects in the barrier. Science 267: 474–475, 1995PubMedCrossRefGoogle Scholar
  19. 19.
    Fournier NC, Rahim M: Control of energy production in the heart: A new function for fatty acid binding protein. Biochemistry 24: 2387–2396, 1985PubMedCrossRefGoogle Scholar
  20. 20.
    Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery CA Jr, Butel JS, Bradley A: Mice deficient for p 53 are developmentally normal but susceptible to spontaneous tumours. Nature 356: 215–221, 1992PubMedCrossRefGoogle Scholar
  21. 21.
    Rappolee DA, Mark D, Banda MJ, Werb Z: Wound macrophages express TGF-alpha and other growth factors in vivo: Analysis by mRNA phenotyping. Science 241: 708–712, 1988PubMedCrossRefGoogle Scholar
  22. 22.
    Marikovsky M, Breuing K, Liu PY, Eriksson E, Higashiyama S, Farber P, Abraham J, Klagsbrun M: Appearance of heparin-binding EGF-like growth factor in wound fluid as a response to injury. Proc Natl Acad Sci USA 90: 3889–3893, 1993PubMedCrossRefGoogle Scholar
  23. 23.
    Werner S, Peters KG, Longaker MT, Fuller-Pace F, Banda MJ, Williams LT: Large induction of keratinocyte growth factor expression in the dermis during wound healing. Proc Natl Acad Sci USA 89: 6896–6900, 1992PubMedCrossRefGoogle Scholar
  24. 24.
    Hulsey TK, O'Neill JA, Neblett WR, Meng HC: Experimental wound healing in essential fatty acid deficiency. J Pediatr Surg 15: 505–508, 1980PubMedCrossRefGoogle Scholar
  25. 25.
    Caffrey BB, Jonsson HT Jr: Role of essential fatty acids in cutaneous wound healing in rats. Prog Lipid Res 20: 641–647, 1981PubMedCrossRefGoogle Scholar
  26. 26.
    Murphy EJ: L-FABP and I-FABP expression increase NBD-stearate uptake and cytoplasmic diffusion in L cells. Am J Physiol 275: G244–G249, 1998PubMedGoogle Scholar
  27. 27.
    Schaap FG, Binas B, Danneberg H, van der Vusse GJ, Glatz JF: Impaired long-chain fatty acid utilization by cardiac myocytes isolated from mice lacking the heart-type fatty acid binding protein gene. Circ Res 85: 329–337, 1999PubMedGoogle Scholar
  28. 28.
    Michalik L, Desvergne B, Tan NS, Basu-Modak S, Escher P, Rieusset J, Peters JM, Kaya G, Gonzalez FJ, Zakany J, Metzger D, Chambon P, Duboule D, Wahli W: Impaired skin wound healing in peroxisome proliferator-activated receptor (PPAR)alpha and PPARbeta mutant mice. J Cell Biol 154: 799–814, 2001PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Yoshiyuki Kusakari
    • 1
  • Eisaku Ogawa
    • 1
  • Yuji Owada
    • 2
  • Noriko Kitanaka
    • 2
  • Hiroshi Watanabe
    • 1
  • Michiyo Kimura
    • 1
  • Hachiro Tagami
    • 1
  • Hisatake Kondo
    • 2
  • Setsuya Aiba
    • 1
  • Ryuhei Okuyama
    • 1
    • 3
    Email author
  1. 1.Department of DermatologyTohoku University Graduate School of MedicineTohokuJapan
  2. 2.Department of HistologyTohoku University Graduate School of MedicineTohokuJapan
  3. 3.Department of DermatologyTohoku University Graduate School of MedicineAoba-kuJapan

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