Stimulation of all epithelial elements during skin regeneration by keratinocyte growth factor.

Abstract

SummaryKeratinocyte growth factor (KGF), a recently discovered 18.9 kD member of the fibroblast growth factor family has been shown to selectively induce keratinocyte proliferation and differentiation in tissue culture. To explore its potential stimulating keratinocyte growth and differentiation in vivo, we analyzed for the influence of KGF on epithelial derived elements within a wound created through the cartilage on the rabbit ear. KGF accelerated reepithelialization (p = 0.004) and increased the thickness of the epithelium (p = 0.0005) when 4-40/~g/cm 2 recombinant KGF was added at the time of wounding. The regenerating epidermis showed normal differentiation as detected by cytokeratin immunostaining. Remarkably, however, KGF stimulated proliferation and differentiation of early progenitor cells within hair follicles and sebaceous glands in the wound bed and adjacent dermis. There was a transient but highly significant increase in specific labeling of cycling cells in both basal and suprabasal layers that extended into the spinous layer of the regenerating epidermis. As an indication of specificity, the inflammatory cells and fibroblasts within the wound were not influenced by KGF. The results indicate that KGF is unique in its ability to accelerate reepithelialization and dermal regeneration by targeting multiple epithelial elements within the skin. These results suggest that KGF may induce specific epithelial progenitor cell lineages within the skin to proliferate and differentiate, and thus may be a critical determinant of regeneration of skin. Furthermore, these findings illustrate the potential capacity of this system to analyze epithelial differentiation programs and disorders of epidermis, dermal glandular elements, and hair follicles.

Keratinocyte growth factor ameliorates acute graft-versus-host disease in a novel nonmyeloablative haploidentical transplantation model

“…This might be explained by the overall effect of KGF on all epithelial elements, including hair follicles. 26,48 It is worth mentioning that this fur condition is only temporary and returns to normal within a few days after cessation of the treatment. Considering this mild side effect, the effect on the small intestine and taking into account some reports about KGF post-treatment not adding to overall survival, 46,31 it might be wise to examine whether a short pretransplant KGF treatment is sufficient to prevent lethal GVHD in our setting.…”

“…KGF is a member of the fibroblast growth factor family, also designated as FGF-7, that specifically influences epithelial cells in vivo and in vitro. 25 KGF induces proliferation in keratinocytes, 26 type II pneumocytes, 27 hepatocytes and gastrointestinal (GI) epithelial cells. 28 It has also been demonstrated that KGF can enhance survival of crypt stem cells 29 and might thus be used to protect the GI mucosa when administered prior to conditioning.…”

Pattern of keratinocyte growth factor and keratinocyte growth factor receptor expression during mouse fetal development suggests a role in mediating morphogenetic mesenchymal‐epithelial interactions

“…However, other experimental approaches will be required to fully define the precise nature of KGF involvement in epithelial development. In this regard, earlier cell and organ culture studies have demonstrated that KGF is a paracrine mitogen for epithelial cells from a variety of different sources (Aaronson et al, 1991;Marchese et al, 1990;Pierce et al, 1994;Rubin et al, 1989;Ulich et al, 1994), as well as a morphogen in the ductal branching morphogenesis of the neonatal mouse seminal vesicle (Alarid et al, 1994) and the neonatal rat prostate (Sugimura et al, 1993). The extension of similar studies to other organ systems will provide a powerful approach in further elucidating the multiple roles of KGF during development.…”

Prophylaxis and treatment of chemo- and radiotherapy-induced oral mucositis – are there new strategies?

“…This cytokine seems to specifically act on epithelial cells, inducing proliferation, differentiation and migration. [143][144][145] After skin injury mRNA transcription for KGF is induced in the dermis of the wound margin and in the hypodermis below the wound ground. Messenger RNA for the KGF receptor is induced in the epidermis.…”