Hyperglycemia Promotes Schwann Cell De-differentiation and De-myelination via Sorbitol Accumulation and Igf1 Protein Down-regulation

Hao, W.; Tashiro, S.; Hasegawa, T.; Sato, Y.; Kobayashi, T.; Tando, T.; Katsuyama, E.; Fujie, A.; Watanabe, R.; Morita, M.; Miyamoto, K.; Morioka, H.; Nakamura, M.; Matsumoto, M.; Amizuka, N.; Toyama, Y.; Miyamoto, T

Hyperglycemia Promotes Schwann Cell De-differentiation and De-myelination via Sorbitol Accumulation and Igf1 Protein Down-regulation

Hao, W.; Tashiro, S.; Hasegawa, T. et al.

The Journal of biological chemistry, 2015, 290(28), 17106-17115

Permalink : https://hdl.handle.net/2115/72270

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アクセス権	open access
URI	https://hdl.handle.net/2115/72270
タイトル	Hyperglycemia Promotes Schwann Cell De-differentiation and De-myelination via Sorbitol Accumulation and Igf1 Protein Down-regulation
著者	Hao, W. ; Tashiro, S. ; Hasegawa, T. ; Sato, Y. ; Kobayashi, T. ; Tando, T. ; Katsuyama, E. ; Fujie, A. ; Watanabe, R. ; Morita, M. ; Miyamoto, K. ; Morioka, H. ; Nakamura, M. ; Matsumoto, M. ; Amizuka, N. ; Toyama, Y. ; Miyamoto, T
著者名 Hao, W.
著者名 Tashiro, S.
e-Rad_Researcher 50739349 著者名 Hasegawa, T.
著者名 Sato, Y.
著者名 Kobayashi, T.
著者名 Tando, T.
著者名 Katsuyama, E.
著者名 Fujie, A.
著者名 Watanabe, R.
著者名 Morita, M.
著者名 Miyamoto, K.
著者名 Morioka, H.
著者名 Nakamura, M.
著者名 Matsumoto, M.
e-Rad_Researcher 30242431 著者名 Amizuka, N.
著者名 Toyama, Y.
著者名 Miyamoto, T
言語	英語
キーワード	cell differentiation
	cell metabolism
	diabetes
	differentiation
	Schwann cells
	vitamin D
発行日	2015-07-10
出版者	American Society for Biochemistry and Molecular Biology
収録物名	The Journal of biological chemistry
巻(号)	290(28)
ページ	17106-17115
抄録	Diabetes mellitus (DM) is frequently accompanied by complications, such as peripheral nerve neuropathy. Schwann cells play a pivotal role in regulating peripheral nerve function and conduction velocity; however, changes in Schwann cell differentiation status in DM are not fully understood. Here, we report that Schwann cells de-differentiate into immature cells under hyperglycemic conditions as a result of sorbitol accumulation and decreased Igf1 expression in those cells. We found that de-differentiated Schwann cells could be re-differentiated in vitro into mature cells by treatment with an aldose reductase inhibitor, to reduce sorbitol levels, or with vitamin D3, to elevate Igf1 expression. In vivo DM models exhibited significantly reduced nerve function and conduction, Schwann cell de-differentiation, peripheral nerve de-myelination, and all conditions were significantly rescued by aldose reductase inhibitor or vitamin D3 administration. These findings reveal mechanisms underlying pathological changes in Schwann cells seen in DM and suggest ways to treat neurological conditions associated with this condition.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	This research was originally published in the Journal of Biological Chemistry. Wu Hao, Syoichi Tashiro, Tomoka Hasegawa, Yuiko Sato, Tami Kobayashi, Toshimi Tando, Eri Katsuyama, Atsuhiro Fujie, Ryuichi Watanabe, Mayu Morita, Kana Miyamoto, Hideo Morioka, Masaya Nakamura, Morio Matsumoto, Norio Amizuka, Yoshiaki Toyama, and Takeshi Miyamoto. Hyperglycemia Promotes Schwann Cell De-differentiation and De-myelination via Sorbitol Accumulation and Igf1 Protein Down-regulation. J. Biol. Chem. 2015; Vol 290(28): 17106-17115. © the American Society for Biochemistry and Molecular Biology.
PISSN	0021-9258
NCID	AA00251083
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1074/jbc.M114.631291