中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (10): 1706-1712.doi: 10.4103/1673-5374.167773

• 原著:神经损伤修复保护与再生 • 上一篇    

激活许旺细胞炎症反应:高迁移率族蛋白1及其受体信号通路

  

  • 收稿日期:2015-06-20 出版日期:2015-10-28 发布日期:2015-10-28
  • 基金资助:

    国家自然科学基金(No. 31471011);973课题(2014CB542202);江苏省自然科学基(BK20131203);江苏高校优势学科建设工程资助项目

The HMGB1 signaling pathway activates the inflammatory response in Schwann cells

Li-li Man1, #, Fan Liu2, #, Ying-jie Wang1, Hong-hua Song3, Hong-bo Xu4, Zi-wen Zhu1, Qing Zhang1, Yong-jun Wang1,*   

  1. 1 Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China
    2 Department of Oncology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
    3 Department of Pediatrics, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
    4 Medical College, Nantong University, Nantong, Jiangsu Province, China
  • Received:2015-06-20 Online:2015-10-28 Published:2015-10-28
  • Contact: Yong-jun Wang, Ph.D.,wyjbs@ntu.edu.cn.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 31471011; a grant from the National Program on Key Basic Research Project of China (973 Program),No. 2014CB542202; the Natural Science Foundation of Jiangsu Province of China, No. BK20131203; a grant from the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) of China.

摘要:

许旺细胞不仅是成髓鞘细胞,还可被视为广泛表达天然模式识别受体Toll样受体的免疫活性细胞。周围神经损伤可激活许旺细胞炎症反应,但特异性内源损伤相关分子模式分子如何参与这一作用尚不完全清楚。实验证实关键的损伤相关分子模式分子--高迁移率族蛋白1(HMGB1)在大鼠坐骨神经切断后表达上调,并与许旺细胞共定位。高迁移率族蛋白1本身不能提高Toll样受体和晚期糖基化终末产物受体的表达,但可促进许旺细胞迁移。当高迁移率族蛋白1与脂多糖共同刺激许旺细胞时,该蛋白使Toll样受体和晚期糖基化终末产物受体,以及炎症因子的表达增加。实验揭示了激活许旺细胞炎症反应的新分子信号通路,干预该信号通路将有益于损伤周围神经的神经保护。

关键词: 神经再生, 周围神经损伤, 坐骨神经切断, 高迁移率族蛋白1, 许旺细胞, 迁移, 炎症反应, TLRs, DAMPs, 细胞因子

Abstract:

Schwann cells are not only myelinating cells, but also function as immune cells and express numerous innate pattern recognition receptors, including the Toll-like receptors. Injury to peripheral nerves activates an inflammatory response in Schwann cells. However, it is unclear whether specific endogenous damage-associated molecular pattern molecules are involved in the inflammatory response following nerve injury. In the present study, we demonstrate that a key damage-associated molecular pattern molecule, high mobility group box 1 (HMGB1), is upregulated following rat sciatic nerve axotomy, and we show colocalization of the protein with Schw-ann cells. HMGB1 alone could not enhance expression of Toll-like receptors or the receptor for advanced glycation end products (RAGE), but was able to facilitate migration of Schwann cells. When Schwann cells were treated with HMGB1 together with lipopolysaccharide, the expression levels of Toll-like receptors and RAGE, as well as inflammatory cytokines were upregulated. Our novel findings demonstrate that the HMGB1 pathway activates the inflammatory response in Schwann cells following peripheral nerve injury.

Key words: nerve regeneration, peripheral nerve injury, sciatic nerve transection, Schwann cells, HMGB1, migration, inflammatory response, TLRs, peripheral nerves, DAMPs, cytokines, neural regeneration