The Function of KGF in Morphogenesis of Epithelium and Reepithelialization of Wounds

Abstract

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. The skin of transgenic mice was characterized by epidermal atrophy, abnormalities in the hair follicles, and dermal hyperthickening. Upon skin injury, inhibition of KGF receptor signaling reduced the proliferation rate of epidermal keratinocytes at the wound edge, resulting in substantially delayed reepithelialization of the wound.

Neu differentiation factor/heregulin induction by hepatocyte and keratinocyte growth factors

“…Previous reports have demonstrated that the level of KGF dramatically increases in dermal ®broblasts within 24 h after skin injury (Werner et al, 1992), and that impaired KGF receptor signaling in wounded skin results in substantially delayed re-epithelization (Werner et al, 1994). Using the same animal model of skin injury described by Werner et al (1992), we observed the induction of NDF during wound healing after the established peak of KGF induction, suggesting a direct link between the two events.…”

“…Samples were fractionated by 12% SDS ± PAGE, transferred to PVDF membranes, and probed with anti-NDF antibody. Lysate prepared from MDA MB 231 cells was used as a positive control (Werner et al, 1994), and the position of mature NDF (p44) is indicated. (b) Mean DNA synthesis (+s.d.)…”

Liposomal gene transfer of multiple genes is more effective than gene transfer of a single gene

“…From previous experiments, we found that KGF, a 26-28 kDa protein, is an epithelial growth factor that exerts its effects mainly in a paracrine manner and is essential for skin morphogenesis. 12,13 KGF has been shown to stimulate epithelial cell differentiation and it appears to control the proliferative-differentiative program from basal to suprabasal cells in the skin. 14 Moreover, KGF stimulates proliferation and exerts an antiapoptotic effect for epithelial cells, which are of major importance for the post-traumatic wound healing.…”

A Novel Enhancer of the Wound Healing Process

“…12,13 This is functionally important because FGF2 knockout mice have impaired wound healing, 14 and expression of a dominant-negative FGFR2 mutant in keratinocytes of transgenic mice resulted in a severe delay in wound re-epithelialization. 15 Therefore, FGF signaling is obviously required for efficient healing. Thereby, different FGFs are likely to fulfill different functions: FGF2 seems to be particularly important for wound angiogenesis, whereas FGF7, FGF10, and FGF22, whose functions were blocked by the dominant-negative FGFR2 mutant, are important regulators of wound re-epithelialization.…”

“…Thereby, different FGFs are likely to fulfill different functions: FGF2 seems to be particularly important for wound angiogenesis, whereas FGF7, FGF10, and FGF22, whose functions were blocked by the dominant-negative FGFR2 mutant, are important regulators of wound re-epithelialization. 14,15 Because FGF-BP1 binds to multiple FGFs, it may well be involved in all these processes.…”