期刊
BIOMATERIALS
卷 134, 期 -, 页码 64-77出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2017.02.026
关键词
Chitooligosaccharides; Peripheral nerve regeneration; Schwann cells; Chemokines; Microenvironments
资金
- National Major Project of Research and Development [2016YFC1101603]
- Hi-Tech Research and Development Program of China (973 Program) [2014CB542202]
- National Natural Science Foundation of China [81371687, 81671823, 31471011, 81471037]
- Natural Science Research Program of Jiangsu Education Department [14KJB180020, 14KJA180006]
Chitosan-based artificial nerve grafts have been widely employed to repair peripheral nerve defects. Our previous study has shown that chitosan constructed nerve graft not only provides suitable scaffolds for nerve regeneration, its degradation products, chitooligosaccharides (COS), also promote nerve repair. However, the involved mechanisms are still not fully elucidated. In the present study, we observed that pro-inflammatory cytokines, as well as macrophage infiltration, were transiently up-regulated in the injured sciatic nerves which were bridged with silicon tubes filled with COS. Based upon transcriptome analysis, the axis of miR-327/CCL2 in Schwann cells (SCs) was identified as a potential target of COS. The following experiments have confirmed that COS stimulate CCL2 expression by down-regulating miR-327 in SCs. Consequently, the resulting CCL2 induces macrophage migration at injury sites to re-construct microenvironments and thus facilitates nerve regeneration. Collectively, our data provide a theoretical basis for the clinical application of chitosan-based grafts in peripheral nerve regeneration. (C) 2017 Elsevier Ltd. All rights reserved.
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