Effects of keratinocyte growth factor-2 (KGF-2) on wound healing in an ischaemia-impaired rabbit ear model and on scar formation

Keratinocyte growth factor-2 (KGF-2), also described as fibroblast growth f actor-10 (FGF-10), is a member of the fibroblast growth factor family. KGF- 2 shares 57 per cent sequence homology to previously reported KGF-1 (FGF-7) , In skin, both growth factors are expressed in the dermal compartment, KGF -1 and KGF-2 bind to the same receptor with high affinity, the KGFR isoform of FGFR2, which is exclusively expressed by epithelial cells. This study e xamines the in vivo function of topically applied KGF-2 on wound healing us ing an ischaemia-impaired rabbit dermal ulcer model, in young and aged anim als. Histological analysis of the wounds showed that KGF-2 significantly pr omoted re-epithelialization in both young and old animals. Similar results have been observed with KGF-1 in this model. In addition, KGF-2 enhanced gr anulation tissue formation in both young and old rabbits, a biological effe ct not found with KGF-1, suggesting a possible indirect mechanism which enh ances neo-granulation tissue formation. Immunohistological staining of day 7 wounds with proliferating cell nuclear antigen (PCNA) antibody demonstrat ed a significant increase of dermal cell proliferation in KGF-2-treated wou nds compared with placebo wounds. These results suggest a mesenchymal-epith elial interaction that is mediated by a paracrine feedback loop of KGF-2, B ecause of the wound healing impairment observed with ageing, the wound heal ing response to KGF-2 was also studied in ischaemic wounds of aged animals. Administration of KGF-2 led to significant stimulation of epithelial growt h and granulation tissue formation. The effects seen in the old animals wer e delayed compared with the young animals. Lastly, the effect of KGF-2 was examined in a rabbit model of scar formation. Quantification of scar elevat ion index showed no significant differences in scar formation when KGF-2 wa s compared with buffer placebo. Compared with other growth factors, includi ng KGF-1 and TGF-beta which have previously been examined in these models, KGF-2 is the most effective and causes no obvious scarring. Copyright (C) 1 999 John Wiley & Sons, Ltd.