Title: | Hyperglycemia Promotes Schwann Cell De-differentiation and De-myelination via Sorbitol Accumulation and Igf1 Protein Down-regulation |
Authors: | Hao, W. Browse this author |
Tashiro, S. Browse this author |
Hasegawa, T. Browse this author →KAKEN DB |
Sato, Y. Browse this author |
Kobayashi, T. Browse this author |
Tando, T. Browse this author |
Katsuyama, E. Browse this author |
Fujie, A. Browse this author |
Watanabe, R. Browse this author |
Morita, M. Browse this author |
Miyamoto, K. Browse this author |
Morioka, H. Browse this author |
Nakamura, M. Browse this author |
Matsumoto, M. Browse this author |
Amizuka, N. Browse this author →KAKEN DB |
Toyama, Y. Browse this author |
Miyamoto, T Browse this author |
Keywords: | cell differentiation |
cell metabolism |
diabetes |
differentiation |
Schwann cells |
vitamin D |
Issue Date: | 10-Jul-2015 |
Publisher: | American Society for Biochemistry and Molecular Biology |
Journal Title: | The Journal of biological chemistry |
Volume: | 290 |
Issue: | 28 |
Start Page: | 17106 |
End Page: | 17115 |
Publisher DOI: | 10.1074/jbc.M114.631291 |
Abstract: | 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. |
Rights: | 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. |
Type: | article |
URI: | http://hdl.handle.net/2115/72270 |
Appears in Collections: | 歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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