Chitosan Degradation Products Promote Nerve Regeneration by Stimulating Schwann Cell Proliferation via miR-27a/FOXO1 Axis.
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.
Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China.|Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China.
Yongjun
Y
Wang
Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China.|Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China.
Yahong
Y
Zhao
Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China.|Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China.
Cheng
C
Sun
Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China.|Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China.
Wen
W
Hu
Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China.|Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China.
Jing
J
Zhao
Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China.|Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China.
Guicai
G
Li
Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China.|Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China.
Luzhong
L
Zhang
Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China.|Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China.
Mei
M
Liu
Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China.|Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China.
Yan
Y
Liu
Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China.|Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China.
Fei
F
Ding
Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China. yangym702@163.com.|Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China. yangym702@163.com.
Yumin
Y
Yang
Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China. nervegu@ntu.edu.cn.|Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China. nervegu@ntu.edu.cn.
Xiaosong
X
Gu
D000818:Animals; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D048271:Chitosan / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology* / Q000378:metabolism*; D012584:Sciatic Nerve / Q000166:cytology; D000071161:Forkhead Box Protein O1
D048271:Chitosan; D051858:Forkhead Transcription Factors; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; C000594049:MIRN27 microRNA, rat; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1
Biomaterials; Oligosaccharides; Polysaccharides; Regeneration; miRNA