Chondroitin 6-sulphate synthesis is up-regulated in injured CNS, induced by injury-related cytokines and enhanced in axon-growth inhibitory glia.
Chondroitin sulphate proteoglycans (CSPGs) are up-regulated in the CNS after injury and inhibit axon regeneration mainly through their glycosaminoglycan (CS-GAG) chains. We have analysed the mRNA levels of the CS-GAG synthesizing enzymes and measured the CS-GAG disaccharide composition by chromatography and immunocytochemistry. Chondroitin 6-sulfotransferase 1 (C6ST1) is up-regulated in most glial types around cortical injuries, and its sulphated product CS-C is also selectively up-regulated. Treatment with TGFalpha and TGFbeta, which are released after brain injury, promotes the expression of C6ST1 and the synthesis of 6-sulphated CS-GAGs in primary astrocytes. Oligodendrocytes, oligodendrocyte precursors and meningeal cells are all inhibitory to axon regeneration, and all express high levels of CS-GAG, including high levels of 6-sulphated GAG. In axon growth-inhibitory Neu7 astrocytes C6ST1 and 6-sulphated GAGs are expressed at high levels, whereas in permissive A7 astrocytes they are not detectable. These results suggest that the up-regulation of CSPG after CNS injury is associated with a specific sulphation pattern on CS-GAGs, mediating the inhibitory properties of proteoglycans on axonal regeneration.
Properzi
Francesca
F
Centre for Brain Repair, Cambridge University, Forvie Site, Cambridge CB2 2PY, UK.
Carulli
Daniela
D
Asher
Richard A
RA
Muir
Elizabeth
E
Camargo
Luiz M
LM
van Kuppevelt
Toin H
TH
ten Dam
Gerdy B
GB
Furukawa
Yoko
Y
Mikami
Tadishima
T
Sugahara
Kazuyuki
K
Toida
Toshihiko
T
Geller
Herbert M
HM
Fawcett
James W
JW
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000378:metabolism; D001369:Axons / Q000502:physiology*; D015152:Blotting, Northern / Q000379:methods; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D001930:Brain Injuries / Q000201:enzymology*; D039481:CD11b Antigen / Q000378:metabolism; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000235:genetics / Q000378:metabolism*; D002845:Chromatography / Q000379:methods; D004622:Embryo, Mammalian; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007797:Laminin / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology*; D009457:Neuroglia / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013234:Stem Cells; D013997:Time Factors; D015854:Up-Regulation; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D039481:CD11b Antigen; D002809:Chondroitin Sulfates; D005904:Glial Fibrillary Acidic Protein; D006025:Glycosaminoglycans; D007797:Laminin; D011509:Proteoglycans; D012333:RNA, Messenger; D000099216:Chondroitin Sulfate Proteoglycan 4