TY - JOUR
T1 - Chondroitin 6-sulphate synthesis is up-regulated in injured CNS, induced by injury-related cytokines and enhanced in axon-growth inhibitory glia
AU - Properzi, Francesca
AU - Carulli, Daniela
AU - Asher, Richard A.
AU - Muir, Elizabeth
AU - Camargo, Luiz M.
AU - Van Kuppevelt, Toin H.
AU - Ten Dam, Gerdy B.
AU - Furukawa, Yoko
AU - Mikami, Tadishima
AU - Sugahara, Kazuyuki
AU - Toida, Toshihiko
AU - Geller, Herbert M.
AU - Fawcett, James W.
PY - 2005/1
Y1 - 2005/1
N2 - 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 TGFα and TGFβ, 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.
AB - 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 TGFα and TGFβ, 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.
UR - http://www.scopus.com/inward/record.url?scp=13444278866&partnerID=8YFLogxK
U2 - 10.1111/j.1460-9568.2005.03876.x
DO - 10.1111/j.1460-9568.2005.03876.x
M3 - Article
SN - 0953-816X
VL - 21
SP - 378
EP - 390
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
IS - 2
ER -