Implication of heparan sulfate proteoglycans in diseases

Heparan sulfate proteoglycan (HSPG),a group of macromolecular glycoconjugates expressed on the cell surfaces and in the extracellular matrix (ECM),is essential for animal development and homeostasis.HSPG participates in many important biological activities,mostly through interactions of the side heparan sulfate (HS) polysaccharide chains with a wide range of protein ligands.Cell surface HS interacts with growth factors and their receptors,mediating signal transduction.As a main component of the ECM,HSPG maintains the integrity and architecture of the ECM together with collagens.Heparanase specifically degrades HS,hence affects a range of biological activities and microenvironment of the ECM by cleavage of HS.Accordingly,to uncover the molecular structure of HS and its biological correlation has become very important under normal and disease conditions.Due to the complicated heterogeneous structure of HS,progress on analysis of HS molecular properties and its interaction with proteins has been relatively slow.Recently,with development of advanced technologies,activities in this research field are significantly increased.Given the dramatic expansion of the field in investigation of the physiopathological functions of HSPG and heparanase,we do not endeavor to comprehensively cover all aspects of this development.Excellent reviews dealing with structural,metabolic,and functional aspects of HS,with detailed account of methodological progress regarding HS compositional and sequence analysis,conformational aspects,and HS-protein interactions,have been published (see references).The primary aim of this review is to discuss the roles of HS in diseases with hope to shed light on development of therapeutics targeting HSPGs.