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Chitosan Degradation Products Promote Nerve Regeneration by Stimulating Schwann Cell Proliferation via miR-27a/FOXO1 Axis

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Abstract

Natural polysaccharides are biomaterials widely used for constructing scaffolds in tissue engineering. While natural polysaccharides have been shown to robustly promote tissue regeneration, the underlying molecular mechanism remains largely unknown. Here, we show that chitooligosaccharides (COS), the intermediate products of chitosan degradation, stimulate peripheral nerve regeneration in rats. Our experiment also shows that COS stimulate the proliferation of Schwann cells (SCs) during nerve regeneration. By analyzing the transcriptome and gene regulatory network, we identified the miR-27a/FOXO1 axis as the main signaling pathway for mediating the proliferative effects of COS on SCs. COS increase the expression level of miR-27a and cause a reduction of FOXO1, which subsequently accelerates the cell cycle and stimulates SC proliferation to stimulate nerve regeneration. These findings define a basic pathway for oligosaccharides-mediated cell proliferation and reveal a novel aspect of polysaccharide biomaterials in tissue engineering.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (Grant Nos. 81371687, 81171457, 81130080, and 31471011), the Ministry of Science and Technology of China Grants (973 Program, 2014CB542202; 863 Program, 2012AA020502), and the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions.

Conflict of Interest

The authors have declared that no competing interests exist.

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Authors and Affiliations

  1. Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China

    Yongjun Wang, Yahong Zhao, Cheng Sun, Wen Hu, **g Zhao, Guicai Li, Luzhong Zhang, Mei Liu, Yan Liu, Fei Ding, Yumin Yang & **aosong Gu

  2. Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China

    Yongjun Wang, Yahong Zhao, Cheng Sun, Wen Hu, **g Zhao, Guicai Li, Luzhong Zhang, Mei Liu, Yan Liu, Fei Ding, Yumin Yang & **aosong Gu

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  1. Yongjun Wang
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  2. Yahong Zhao
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  3. Cheng Sun
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  4. Wen Hu
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Corresponding authors

Correspondence to Yumin Yang or **aosong Gu.

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Yongjun Wang and Yahong Zhao contributed equally to this work.

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Table S1

172 differentially expressed miRNAs (XLS 70 kb)

Table S2

4, 399 differentially expressed mRNAs (XLS 810 kb)

Table S3

Differentially expressed miRNAs with significant P value and their corresponding targets (XLS 21 kb)

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Wang, Y., Zhao, Y., Sun, C. et al. Chitosan Degradation Products Promote Nerve Regeneration by Stimulating Schwann Cell Proliferation via miR-27a/FOXO1 Axis. Mol Neurobiol 53, 28–39 (2016). https://doi.org/10.1007/s12035-014-8968-2

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  • DOI: https://doi.org/10.1007/s12035-014-8968-2

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