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The Beneficial Effect of Chitooligosaccharides on Cell Behavior and Function of Primary Schwann Cells is Accompanied by Up-Regulation of Adhesion Proteins and Neurotrophins

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Abstract

Chitosan-based tissue engineered nerve grafts are successfully used for bridging peripheral nerve gaps. The biodegradation products of chitosan are water-dissolvable chitooligosaccharides (COSs), which have been shown to support peripheral nerve regeneration. In this study, we aimed to examine in vitro interactions between COSs and Schwann cells (SCs), the principal glial cells in the peripheral nervous system. Treatment of primary SCs with COSs enhanced cell survival and promoted cell proliferation in a dose-dependent manner (0.25–1.0 mg/ml), as determined by real-time cell analyzer-based assay, cell growth assay, cell cycle analysis, and EdU incorporation. Western blot analysis and immunocytochemistry with antibodies against MBP and MAG (two myelin-specific markers) showed that COSs enhanced axonal myelination in a co-culture system consisting of SCs and dorsal root ganglia (DRGs). Furthermore, we observed that COSs enhanced the protein expression of N-cadherin and β-catenin in primary SCs, and also increased the release of BDNF and NGF in co-culture of SCs with DRGs. And we also noted that knockdown of N-cadherin in primary SCs reduced COSs-induced increase in cell proliferation. Our findings suggested that beneficial effects of COSs on cell behavior and functions of primary SCs might be accompanied by up-regulation of adhesion proteins and neurotrophins, thus providing a new insight into the supportive role of COSs during peripheral nerve regeneration.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (Grant No. 81101159), General Natural Science Research Project of Colleges and Universities of Jiangsu Province (Grant No. 12KJB310010), and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). We thank Professor Jie Liu for assistance in manuscript preparation.

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Authors and Affiliations

  1. Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, Jiangsu, People’s Republic of China

    Maorong Jiang, Qiong Cheng, Wenfeng Su, Caiping Wang, Yuming Yang, Zheng Cao & Fei Ding

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  1. Maorong Jiang
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  2. Qiong Cheng
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  3. Wenfeng Su
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Correspondence to Zheng Cao or Fei Ding.

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Maorong Jiang and Qiong Cheng contributed equally to this work.

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Jiang, M., Cheng, Q., Su, W. et al. The Beneficial Effect of Chitooligosaccharides on Cell Behavior and Function of Primary Schwann Cells is Accompanied by Up-Regulation of Adhesion Proteins and Neurotrophins. Neurochem Res 39, 2047–2057 (2014). https://doi.org/10.1007/s11064-014-1387-y

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