Keratinocyte growth factor signalling: a mathematical model of dermal-epidermal interaction in epidermal wound healing.
A wealth of growth factors are known to regulate the various cell functions involved in the repair process. An understanding of their therapeutic value is essential to achieve improved wound healing. Keratinocyte growth factor (KGF) seems to have a unique role as a mediator of mesenchymal-epithelial interactions: it originates from mesenchymal cells, yet acts exclusively on epithelial cells. In this paper, we study KGF's role in epidermal wound healing, since its production is substantially up-regulated after injury. We begin by modelling the dermal-epidermal signalling mechanism of KGF to investigate how this extra production affects the signal range. We then incorporate the effect of KGF on cell proliferation, and using travelling wave analysis we obtain an approximation for the rate of healing. Our modelling shows that the large up-regulation of KGF post-wounding extends the KGF signal range but is above optimal for the rate of wound closure. We predict that other functions of KGF may be more important than its role as a mitogen for the healing process.
Wearing
H J
HJ
Centre for Theoretical Modelling in Medicine, Department of Mathematics, Heriot-Watt University, Edinburgh, UK. helenw@ma.hw.ac.uk
Sherratt
J A
JA
D002450:Cell Communication / Q000502:physiology; D002455:Cell Division; D002465:Cell Movement; D003198:Computer Simulation; D004817:Epidermis / Q000187:drug effects / Q000293:injuries / Q000502:physiology*; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D015398:Signal Transduction / Q000502:physiology*; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
C496453:FGF7 protein, human; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors