Fibroblast exosomal TFAP2C induced by chitosan oligosaccharides promotes peripheral axon regeneration via the miR-132-5p/CAMKK1 axis
Chitosan and its degradation product, oligosaccharides, have been shown to facilitate peripheral nerve regeneration. However, the underlying mechanisms are not well understood. In this study, we analyzed the protein expression profiles in sciatic nerves after injury using proteomics. A group of prot...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2023-08-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X23000798 |
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| author | Yahong Zhao Jina Liu Sha Liu Panpan Yang Yunyun Liang Jinyu Ma Susu Mao Cheng Sun Yumin Yang |
| author_facet | Yahong Zhao Jina Liu Sha Liu Panpan Yang Yunyun Liang Jinyu Ma Susu Mao Cheng Sun Yumin Yang |
| author_sort | Yahong Zhao |
| collection | DOAJ |
| description | Chitosan and its degradation product, oligosaccharides, have been shown to facilitate peripheral nerve regeneration. However, the underlying mechanisms are not well understood. In this study, we analyzed the protein expression profiles in sciatic nerves after injury using proteomics. A group of proteins related to exosome packaging and transport is up-regulated by chitosan oligosaccharides (COS), implying that exosomes are involved in COS-induced peripheral nerve regeneration. In fact, exosomes derived from fibroblasts (f-EXOs) treated with COS significantly promoted axon extension and regeneration. Exosomal protein identification and functional studies, revealed that TFAP2C is a key factor in neurite outgrowth induced by COS-f-EXOs. Furthermore, we showed that TFAP2C targets the pri-miRNA-132 gene and represses miR-132-5p expression in dorsal root ganglion neurons. Camkk1 is a downstream substrate of miR-132-5p that positively affects axon extension. In rats, miR-132-5p antagomir stimulates CAMKK1 expression and improves axon regeneration and functional recovery in sciatic nerves after injury. Our data reveal the mechanism for COS in axon regeneration, that is COS induce fibroblasts to produce TFAP2C-enriched EXOs, which are then transferred into axons to promote axon regeneration via miR-132-5p/CAMKK1. Moreover, these results show a new facet of fibroblasts in axon regeneration in peripheral nerves. |
| first_indexed | 2024-04-10T04:34:40Z |
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| id | doaj.art-179f1a01b3e14114947ceb1fe2d80405 |
| institution | Directory Open Access Journal |
| issn | 2452-199X |
| language | English |
| last_indexed | 2024-04-10T04:34:40Z |
| publishDate | 2023-08-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj.art-179f1a01b3e14114947ceb1fe2d804052023-03-10T04:35:46ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2023-08-0126249263Fibroblast exosomal TFAP2C induced by chitosan oligosaccharides promotes peripheral axon regeneration via the miR-132-5p/CAMKK1 axisYahong Zhao0Jina Liu1Sha Liu2Panpan Yang3Yunyun Liang4Jinyu Ma5Susu Mao6Cheng Sun7Yumin Yang8Key Laboratory of Neuroregeneration of Jiangsu Province and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, 19 Qixiu Road, Nantong, Jiangsu, 226001, ChinaKey Laboratory of Neuroregeneration of Jiangsu Province and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, 19 Qixiu Road, Nantong, Jiangsu, 226001, ChinaKey Laboratory of Neuroregeneration of Jiangsu Province and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, 19 Qixiu Road, Nantong, Jiangsu, 226001, ChinaSchool of Medicine, Nantong University, 19 Qixiu Road, Nantong, Jiangsu, 226001, ChinaKey Laboratory of Neuroregeneration of Jiangsu Province and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, 19 Qixiu Road, Nantong, Jiangsu, 226001, ChinaKey Laboratory of Neuroregeneration of Jiangsu Province and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, 19 Qixiu Road, Nantong, Jiangsu, 226001, ChinaKey Laboratory of Neuroregeneration of Jiangsu Province and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, 19 Qixiu Road, Nantong, Jiangsu, 226001, ChinaKey Laboratory of Neuroregeneration of Jiangsu Province and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, 19 Qixiu Road, Nantong, Jiangsu, 226001, China; Corresponding author.Key Laboratory of Neuroregeneration of Jiangsu Province and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, 19 Qixiu Road, Nantong, Jiangsu, 226001, China; Corresponding author.Chitosan and its degradation product, oligosaccharides, have been shown to facilitate peripheral nerve regeneration. However, the underlying mechanisms are not well understood. In this study, we analyzed the protein expression profiles in sciatic nerves after injury using proteomics. A group of proteins related to exosome packaging and transport is up-regulated by chitosan oligosaccharides (COS), implying that exosomes are involved in COS-induced peripheral nerve regeneration. In fact, exosomes derived from fibroblasts (f-EXOs) treated with COS significantly promoted axon extension and regeneration. Exosomal protein identification and functional studies, revealed that TFAP2C is a key factor in neurite outgrowth induced by COS-f-EXOs. Furthermore, we showed that TFAP2C targets the pri-miRNA-132 gene and represses miR-132-5p expression in dorsal root ganglion neurons. Camkk1 is a downstream substrate of miR-132-5p that positively affects axon extension. In rats, miR-132-5p antagomir stimulates CAMKK1 expression and improves axon regeneration and functional recovery in sciatic nerves after injury. Our data reveal the mechanism for COS in axon regeneration, that is COS induce fibroblasts to produce TFAP2C-enriched EXOs, which are then transferred into axons to promote axon regeneration via miR-132-5p/CAMKK1. Moreover, these results show a new facet of fibroblasts in axon regeneration in peripheral nerves.http://www.sciencedirect.com/science/article/pii/S2452199X23000798peripheral nerveschitosan oligosaccharidesfibroblast exosomesTFAP2Caxon regeneration |
| spellingShingle | Yahong Zhao Jina Liu Sha Liu Panpan Yang Yunyun Liang Jinyu Ma Susu Mao Cheng Sun Yumin Yang Fibroblast exosomal TFAP2C induced by chitosan oligosaccharides promotes peripheral axon regeneration via the miR-132-5p/CAMKK1 axis Bioactive Materials peripheral nerves chitosan oligosaccharides fibroblast exosomes TFAP2C axon regeneration |
| title | Fibroblast exosomal TFAP2C induced by chitosan oligosaccharides promotes peripheral axon regeneration via the miR-132-5p/CAMKK1 axis |
| title_full | Fibroblast exosomal TFAP2C induced by chitosan oligosaccharides promotes peripheral axon regeneration via the miR-132-5p/CAMKK1 axis |
| title_fullStr | Fibroblast exosomal TFAP2C induced by chitosan oligosaccharides promotes peripheral axon regeneration via the miR-132-5p/CAMKK1 axis |
| title_full_unstemmed | Fibroblast exosomal TFAP2C induced by chitosan oligosaccharides promotes peripheral axon regeneration via the miR-132-5p/CAMKK1 axis |
| title_short | Fibroblast exosomal TFAP2C induced by chitosan oligosaccharides promotes peripheral axon regeneration via the miR-132-5p/CAMKK1 axis |
| title_sort | fibroblast exosomal tfap2c induced by chitosan oligosaccharides promotes peripheral axon regeneration via the mir 132 5p camkk1 axis |
| topic | peripheral nerves chitosan oligosaccharides fibroblast exosomes TFAP2C axon regeneration |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X23000798 |
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