FGF-10 and specific structural elements of dermatan sulfate size and sulfation promote maximal keratinocyte migration and cellular proliferation.
Fibroblast growth factor-10 (FGF-10) is essential for epithelial development, while other members of this family, such as FGF-7, are not. FGF-10 is abundantly released into wounds following injury, and likely an essential growth factor required for this process. To evaluate how activation of this growth factor is controlled, multiple glycosaminoglycans were combined with FGF-10 assayed by measurement of the proliferation of cell lines expressing FGF receptor-2-IIIb, or keratinocyte migration in an in vitro wound repair assay. Dermatan sulfate (DS) exhibited greater potency than heparan sulfate or other chondroitin sulfates found in wounds. Structural variants of DS between 10 and 20 disaccharides containing iduronic acid showed maximal capacity to enable FGF-10 receptor stimulation. Furthermore, FGF-10 and DS markedly enhanced migration of keratinocytes in an in vitro wound scratch assay, while FGF-7 or other glycosaminoglycans did not. These data strongly suggest that FGF-10 activity is uniquely important in wound repair and that specific DS structural properties are necessary to promote FGF-10 function. These observations identify a novel interplay between DS and FGF-10 in mediating wound repair.
Radek
Katherine A
KA
Veterans Affairs San Diego Healthcare System, San Diego, California 92161, USA.
Taylor
Kristen R
KR
Gallo
Richard L
RL
D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003871:Dermatan Sulfate / Q000737:chemistry* / Q000494:pharmacology*; D051526:Fibroblast Growth Factor 10 / Q000494:pharmacology*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*
C496463:FGF10 protein, human; D051526:Fibroblast Growth Factor 10; D003871:Dermatan Sulfate