Mechanism of Action of Determining Target Cell Specificity of Endocrine FGF : Regulation by Sulfated Glycosaminoglycans

Abstract

The Fibroblast growth factor (FGF) is responsible for a wide range of bioactivities. Human FGF19 (hFGF19) is expressed in the ileum in response to bile acid, and after secretion into the circulation, it reaches its target organ, the liver, via the portal vein.In the liver, hFGF19 regulates bile acid synthesis. hFGF19 is an endocrine metabolic regulator. Earlier studies have suggested that hFGF19 signals through human FGF receptor 4 (hFGFR4) in the presence of a co-receptor, human βKlotho (hKLB), but its activity and receptor specificity at blood concentrations remain unclear.We explored the components to determine the liver-specific activity of hFGF19 at blood levels. The results suggested that at blood levels, hFGF19 requires sulfated glycosaminoglycans for its signaling via hFGFR4 in the presence of a co-receptor, hKLB, thus establishing specific targeting.