Lack of acidic fibroblast growth factor activation by heparan sulfate species from diabetic rat skin.
The glucosaminoglycans isolated from the skin of control and streptozotocin-diabetic rats were fractionated on ion-exchange chromatography into a heparan sulfate (HS)-like and a heparin-like species. In addition, a low sulfated fraction was isolated from the diabetics. The HS and heparin-like fractions isolated from the diabetics (in contrast to the low sulfated fractions) retained high affinity for the acidic (FGF-1) and basic (FGF-2) fibroblast growth factors. In culture, the fractions purified from the control rats and the heparin-like material isolated from the diabetics mediated the biological activity of both FGFs in a dose-dependent manner. By contrast, the diabetic HS-like fractions promoted the biological activity of FGF-2 but not of FGF-1. The results support the idea that the structural motives in HS required for FGF-1 and FGF-2 mediated receptor signalling are different. They may be relevant to the impaired wound healing observed in the disease.
Bourin
M C
MC
Laboratoire de Recherche sur la Croissance Cellulaire, la Réparation et la Régénération Tissulaire, CNRS URA 1813, Université Paris XII, Créteil, France. bourin@im3.inserm.fr
D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002846:Chromatography, Affinity; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006497:Heparan Sulfate / Q000302:isolation & purification / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008297:Male; D051381:Rats; D012867:Skin / Q000201:enzymology / Q000378:metabolism*; D013311:Streptozocin
D000581:Amidohydrolases; D016220:Fibroblast Growth Factor 1; D016222:Fibroblast Growth Factor 2; D006497:Heparan Sulfate; D013311:Streptozocin; C023079:N-acetylglucosamine deacetylase