Modulation of keratinocyte growth factor and its receptor in reepithelializing human skin.
We investigated the expression and distribution of keratinocyte growth factor (KGF) (FGF-7) and its receptor (KGFR) during reepithelialization of human skin. KGF mRNA levels increased rapidly by 8-10-fold and remained elevated for several days. In contrast, KGFR transcript levels decreased early but were significantly elevated by 8-9 d. A KGF-immunoglobulin G fusion protein (KGF-HFc), which specifically and sensitively detects the KGFR, localized the receptor to differentiating keratinocytes of control epidermis, but revealed a striking decrease in receptor protein expression during the intermediate period of reepithelization. Suramin, which blocked KGF binding and stripped already bound KGF from its receptor, failed to unmask KGFRs in tissue sections from the intermediate phase of wound repair. The absence of KGFR protein despite increased KGFR transcript levels implies functional receptor downregulation in the presence of increased KGF. This temporal modulation of KGF and KGFRs provides strong evidence for the functional involvement of KGF in human skin reepithelialization.
Marchese
C
C
National Institute for Cancer Research, University of Rome La Sapienza, Italy.
Chedid
M
M
Dirsch
O R
OR
Csaky
K G
KG
Santanelli
F
F
Latini
C
C
LaRochelle
W J
WJ
Torrisi
M R
MR
Aaronson
S A
SA
D000328:Adult; D002454:Cell Differentiation; D015536:Down-Regulation; D004817:Epidermis / Q000187:drug effects / Q000502:physiology*; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D005786:Gene Expression Regulation / Q000187:drug effects; D005803:Genes, Immunoglobulin; D006133:Growth Substances / Q000096:biosynthesis*; D006801:Humans; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor; D017978:Receptors, Growth Factor / Q000096:biosynthesis*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D016038:Skin Transplantation; D013498:Suramin / Q000494:pharmacology; D014945:Wound Healing / Q000235:genetics*
C496453:FGF7 protein, human; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D017978:Receptors, Growth Factor; D011993:Recombinant Fusion Proteins; D051523:Fibroblast Growth Factor 7; D013498:Suramin; D005346:Fibroblast Growth Factors; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor