Dermatan sulfate binds and potentiates activity of keratinocyte growth factor (FGF-7).
FGF-7 is induced after injury and induces the proliferation of keratinocytes. Like most members of the FGF family, the activity of FGF-7 is strongly influenced by binding to heparin, but this glycosaminoglycan is absent on keratinocyte cell surfaces and minimally present in the wound environment. In this investigation we compared the relative activity of heparan sulfate and chondroitin sulfate B (dermatan sulfate), glycosaminoglycans that are present in wounds. A lymphoid cell line (BaF/KGFR) containing the FGF-7 receptor (FGFR2 IIIb) was treated with FGF-7 and with various glycosaminoglycans. FGF-7 did not support cell proliferation in the absence of glycosaminoglycan or with addition of heparan sulfate or chondroitin sulfate A/C but did stimulate BaF/KGFR division in the presence of dermatan sulfate or highly sulfated low molecular weight fractions of dermatan. Dermatan sulfate also enabled FGF-7-dependent phosphorylation of mitogen-activated protein kinase and promoted binding of radiolabeled FGF-7 to FGFR2 IIIb. In addition, dermatan sulfate and FGF-7 stimulated growth of normal keratinocytes in culture. Thus, dermatan sulfate, the predominant glycosaminoglycan in skin, is the principle cofactor for FGF-7.
Trowbridge
Janet M
JM
Division of Dermatology, Department of Medicine, University of California and Veterans Affairs Medical Center, San Diego, California 92161, USA.
Rudisill
Jennifer A
JA
Ron
Dina
D
Gallo
Richard L
RL
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D003871:Dermatan Sulfate / Q000494:pharmacology*; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000494:pharmacology / Q000502:physiology*; D006025:Glycosaminoglycans / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008214:Lymphocytes; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology; D013552:Swine; D014162:Transfection
C496453:FGF7 protein, human; C496454:Fgf7 protein, mouse; D006025:Glycosaminoglycans; D011994:Recombinant Proteins; D016220:Fibroblast Growth Factor 1; D051523:Fibroblast Growth Factor 7; D003871:Dermatan Sulfate; D005346:Fibroblast Growth Factors