Hyperglycemia promotes Schwann cell de-differentiation and de-myelination via sorbitol accumulation and Igf1 protein down-regulation

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, Takeshi Miyamoto

研究成果: Article査読

38 被引用数 (Scopus)

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 dedifferentiated Schwann cells could be re-differentiated in vitro into mature cells by treatment with an aldose reductase inhibitor, to reduce sorbitol levels, or with vitaminD3, to elevate Igf1 expression. In vivo DM models exhibited significantly reduced nerve function and conduction, Schwann cell de-differentiation, peripheral nerve de-myelination,andall conditionsweresignificantly 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.

本文言語English
ページ(範囲)17106-17115
ページ数10
ジャーナルJournal of Biological Chemistry
290
28
DOI
出版ステータスPublished - 2015 7 10

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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