Regulatory mechanisms for the activity of heparin-binding ligands through heparan sulfate proteoglycan with the specific sufation patterns

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HS octasaccharide library was produced by recombinant HS6ST and HS2ST. FGF-2-dependent signaling was inhibited by 2-O-sulfated HS octasaccharide, whereas the inhibition of FGF-4-dependent signaling required 2-O- and 6-O-sulfated HS octasaccharide. Mast cells derived from HS2ST and HS6ST-1 -2 double knockout mice fetal skin produced 2-O-sulfate- and 6-O-sulfate-deficient heparin, respectively. The deposit of three mast cell-specific proteases were distinctly inhibited in the each mutated mast cells. the collaborated studies with Bulow elucidated that the mutated HS6ST1 gene was involved in patients with idiopathic hypogonadotrophic hypogonadism (IHH).