Chondroitin sulphate N-acetylgalactosaminyl-transferase-1 inhibits recovery from neural injury

Kosei Takeuchi, Nozomu Yoshioka, Susumu Higa Onaga, Yumi Watanabe, Shinji Miyata, Yoshino Wada, Chika Kudo, Masayasu Okada, Kentaro Ohko, Kanako Oda, Toshiya Sato, Minesuke Yokoyama, Natsuki Matsushita, Masaya Nakamura, Hideyuki Okano, Kenji Sakimura, Hitoshi Kawano, Hiroshi Kitagawa, Michihiro Igarashi

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Abstract

Extracellular factors that inhibit axon growth and intrinsic factors that promote it affect neural regeneration. Therapies targeting any single gene have not yet simultaneously optimized both types of factors. Chondroitin sulphate (CS), a glycosaminoglycan, is the most abundant extracellular inhibitor of axon growth. Here we show that mice carrying a gene knockout for CS N-acetylgalactosaminyltransferase-1 (T1), a key enzyme in CS biosynthesis, recover more completely from spinal cord injury than wild-type mice and even chondroitinase ABC-treated mice. Notably, synthesis of heparan sulphate (HS), a glycosaminoglycan promoting axonal growth, is also upregulated in TI knockout mice because HS-synthesis enzymes are induced in the mutant neurons. Moreover, chondroitinase ABC treatment never induces HS upregulation. Taken together, our results indicate that regulation of a single gene, T1, mediates excellent recovery from spinal cord injury by optimizing counteracting effectors of axon regeneration - an extracellular inhibitor of CS and intrinsic promoters, namely, HS-synthesis enzymes.

Original languageEnglish
Article number2740
JournalNature communications
Volume4
DOIs
Publication statusPublished - 2013 Jan 1

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Takeuchi, K., Yoshioka, N., Higa Onaga, S., Watanabe, Y., Miyata, S., Wada, Y., Kudo, C., Okada, M., Ohko, K., Oda, K., Sato, T., Yokoyama, M., Matsushita, N., Nakamura, M., Okano, H., Sakimura, K., Kawano, H., Kitagawa, H., & Igarashi, M. (2013). Chondroitin sulphate N-acetylgalactosaminyl-transferase-1 inhibits recovery from neural injury. Nature communications, 4, [2740]. https://doi.org/10.1038/ncomms3740