Heparan sulphate proteoglycans in glia and in the normal and injured CNS: expression of sulphotransferases and changes in sulphation

Abstract

Heparan sulphate proteoglycans (HSPGs) have multiple functions relevant to the control of the CNS injury response, particularly in modulating the effects of growth factors and localizing molecules that affect axon growth. We examined the pattern of expression and glycanation of HSPGs in the normal and damaged CNS, and in astrocytes and oligodendrocyte precursors because of their participation in the injury reaction. The composition of HS glycosaminoglycan (GAG) chains was analysed by biochemical analysis and by the binding of antibodies that recognize sulphated epitopes. We also measured levels of HS sulphotransferases and syndecans. Compared with oligodendrocytes, oligodendrocyte precursors have more 2-O-sulphation in their HS GAG. This is accompanied by higher expression of the enzyme responsible for 2-O-sulphation, HS 2-O-sulphotransferase (HS2ST) and a fall in syndecan-1. Astrocytes treated with tumour growth factor (TGF)alpha or TGFbeta to mimic the injury response showed upregulation of syndecan-1 and HS2ST correlating with an increase in 2-O-sulphate residues in their HS GAGs. This also correlated with increased staining with AO4B08 anti-GAG antibody that recognizes high sulphation, and reduced staining with RB4EA12 recognizing low sulphation. After injury to the adult rat brain there was an overall increase in the quantity of HSPG around the injury site, mRNA for HS2ST was increased, and the changes in staining with sulphation-specific antibodies were consistent with an increase in 2-O-sulphated HS. Syndecan-1 was upregulated in astrocytes. The major injury-related change, seen in injured brain and cultured glia, was an increase in 2-O-sulphated HS and increased syndecan-1, suggesting novel approaches to modulating scar formation.

Intracerebral chondroitinase ABC and heparan sulfate proteoglycan glypican improve outcome from chronic stroke in rats

“…ChABC also increases axonal regeneration following nigrostriatal tractotomy (13) and improves nerve regeneration (14) and functional recovery after spinal cord injury (15,16) in rats in vivo. Like CSPGs, HSPGs are extracellular proteins that exist in several isoforms (17,18). HSPG isoforms share a conserved glycosaminoglycan side chain, which has more sulfur groups compared with CSPGs.…”

Quantitative and Qualitative Alterations of Heparan Sulfate in Fibrogenic Liver Diseases and Hepatocellular Cancer

“…Differences between healthy organs, as well as those between the healthy and diseased states of the same organ, are attributable to differential expression of the various HSPGs on one hand and to altered regulation of the enzymatic machinery of HS synthesis and modification on the other. Pathologic changes of HSPG composition, as well as of HS synthesis and structure, have been described in non-malignant conditions such as central nervous system injury (Properzi et al 2008) and chronic kidney disease (Lauer et al 2007;Rops et al 2007) and also in malignant tumors such as pancreatic ductal cancer (Korc 2007).…”

Proteoglycans of reactive rat cortical astrocyte cultures: Abundance of N-unsubstituted glucosamine-enriched heparan sulfate

“…A number of HS proteoglycans (HSPGs) are also expressed in the CNS, and are dysregulated following injury (Properzi et al, 2008). HSPGs are found at the cell surface or in the ECM.…”