It has been reported that basic fibroblast growth factor (bFGF) promotes the healing of skin ulceration by inducing fibroblast proliferation, yet the role of bFGF on epidermal barrier function, especially from the perspective of scratch-induced skin abrasion, remains unknown. To this end, we initially developed an epidermal abrasion mouse model induced by scratching with a stainless-steel wire brush, and examined the effects of bFGF on the wound healing induced by skin abrasion. This procedure induced a significant elevation of transepidermal water loss (TEWL) in a scratch-count-dependent manner. This elevated TEWL was significantly decreased following topical application of bFGF to the skin. In addition, bFGF increased the expression of Ki67 in keratinocytes following mechanical scratching. These results suggest that bFGF enhances keratinocyte proliferation, which, in turn, repairs the skin barrier disruption and wounds caused by scratching in mice. Consistently, bFGF stimulated proliferation of normal human epidermal keratinocytes (NHEK). Intriguingly, the effect of bFGF and other growth factors on NHEK proliferation was additive. However, high cell density diminished the effect of bFGF on NHEK proliferation. This particular result can be explained by our observation that FGF receptor mRNA expression in NHEK was low under conditions of high cell density. Our findings suggest that bFGF stimulates keratinocyte proliferation, especially in a lower cell density environment, to repair skin wound in accord with skin barrier recovery.

1.
Elias PM: Skin barrier function. Curr Allergy Asthma Rep 2008;8:299–305.
2.
Moniaga CS, Egawa G, Kawasaki H, Hara-Chikuma M, Honda T, Tanizaki H, Nakajima S, Otsuka A, Matsuoka H, Kubo A, Sakabe J, Tokura Y, Miyachi Y, Amagai M, Kabashima K: Flaky tail mouse denotes human atopic dermatitis in the steady state and by topical application with Dermatophagoides pteronyssinus extract. Am J Pathol 2010;176:2385–2393.
3.
Proksch E, Folster-Holst R, Jensen JM: Skin barrier function, epidermal proliferation and differentiation in eczema. J Dermatol Sci 2006;43:159–169.
4.
Cork MJ, Danby SG, Vasilopoulos Y, Hadgraft J, Lane ME, Moustafa M, Guy RH, Macgowan AL, Tazi-Ahnini R, Ward SJ: Epidermal barrier dysfunction in atopic dermatitis. J Invest Dermatol 2009;129:1892–1908.
5.
Diepgen TL, Agner T, Aberer W, Berth-Jones J, Cambazard F, Elsner P, McFadden J, Coenraads PJ: Management of chronic hand eczema. Contact Derm 2007;57:203–210.
6.
Hoare C, Li Wan Po A, Williams H: Systematic review of treatments for atopic eczema. Health Technol Assess 2000;4:1–191.
7.
Hengge UR, Ruzicka T, Schwartz RA, Cork MJ: Adverse effects of topical glucocorticosteroids. J Am Acad Dermatol 2006;54:1–15; quiz 16–18.
8.
Lampe MA, Burlingame AL, Whitney J, Williams ML, Brown BE, Roitman E, Elias PM: Human stratum corneum lipids: characterization and regional variations. J Lipid Res 1983;24:120–130.
9.
Egawa G, Kabashima K: Skin as a peripheral lymphoid organ: revisiting the concept of skin-associated lymphoid tissues. J Invest Dermatol 2011;131:2178–2185.
10.
Imokawa G, Abe A, Jin K, Higaki Y, Kawashima M, Hidano A: Decreased level of ceramides in stratum corneum of atopic dermatitis: an etiologic factor in atopic dry skin? J Invest Dermatol 1991;96:523–526.
11.
Saksela O, Moscatelli D, Rifkin DB: The opposing effects of basic fibroblast growth factor and transforming growth factor beta on the regulation of plasminogen activator activity in capillary endothelial cells. J Cell Biol 1987;105:957–963.
12.
Gospodarowicz D, Ferrara N, Schweigerer L, Neufeld G: Structural characterization and biological functions of fibroblast growth factor. Endocr Rev 1987;8:95–114.
13.
Ono I, Akasaka Y, Kikuchi R, Sakemoto A, Kamiya T, Yamashita T, Jimbow K: Basic fibroblast growth factor reduces scar formation in acute incisional wounds. Wound Repair Regen 2007;15:617–623.
14.
Robson MC, Phillips LG, Lawrence WT, Bishop JB, Youngerman JS, Hayward PG, Broemeling LD, Heggers JP: The safety and effect of topically applied recombinant basic fibroblast growth factor on the healing of chronic pressure sores. Ann Surg 1992;216:401–406.
15.
O’Keefe EJ, Chiu ML, Payne RE Jr: Stimulation of growth of keratinocytes by basic fibroblast growth factor. J Invest Dermatol 1988;90:767–769.
16.
Honma Y, Arai I, Sakurai T, Futaki N, Hashimoto Y, Sugimoto M, Nakanishi Y, Nakaike S: Effects of indomethacin and dexamethasone on mechanical scratching-induced cutaneous barrier disruption in mice. Exp Dermatol 2006;15:501–508.
17.
Nakajima S, Honda T, Sakata D, Egawa G, Tanizaki H, Otsuka A, Moniaga CS, Watanabe T, Miyachi Y, Narumiya S, Kabashima K: Prostaglandin i2-ip signaling promotes th1 differentiation in a mouse model of contact hypersensitivity. J Immunol 2010;184:5595–5603.
18.
Kabashima K, Sakabe J, Yoshiki R, Tabata Y, Kohno K, Tokura Y: Involvement of wnt signaling in dermal fibroblasts. Am J Pathol 2010;176:721–732.
19.
Ornitz DM, Xu J, Colvin JS, McEwen DG, MacArthur CA, Coulier F, Gao G, Goldfarb M: Receptor specificity of the fibroblast growth factor family. J Biol Chem 1996;271:15292–15297.
20.
Greenhalgh DG, Sprugel KH, Murray MJ, Ross R: PDGF and FGF stimulate wound healing in the genetically diabetic mouse. Am J Pathol 1990;136:1235–1246.
21.
Tsuboi R, Shi CM, Rifkin DB, Ogawa H: A wound healing model using healing-impaired diabetic mice. J Dermatol 1992;19:673–675.
22.
Tsuboi R, Rifkin DB: Recombinant basic fibroblast growth factor stimulates wound healing in healing-impaired db/db mice. J Exp Med 1990;172:245–251.
23.
Hebda PA, Klingbeil CK, Abraham JA, Fiddes JC: Basic fibroblast growth factor stimulation of epidermal wound healing in pigs. J Invest Dermatol 1990;95:626–631.
24.
Sogabe Y, Abe M, Yokoyama Y, Ishikawa O: Basic fibroblast growth factor stimulates human keratinocyte motility by RAC activation. Wound Repair Regen 2006;14:457–462.
25.
Yang J, Meyer M, Muller AK, Bohm F, Grose R, Dauwalder T, Verrey F, Kopf M, Partanen J, Bloch W, Ornitz DM, Werner S: Fibroblast growth factor receptors 1 and 2 in keratinocytes control the epidermal barrier and cutaneous homeostasis. J Cell Biol 2010;188:935–952.
26.
Smith EW: Do we need new and different glucocorticoids? A re-appraisal of the various congeners and potential alternatives. Curr Probl Dermatol 1993;21:1–10.
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