Potential application of let-7a antagomir in injured peripheral nerve regeneration
Neurotrophic factors, particularly nerve growth factor, enhance neuronal regeneration. However, the in vivo applications of nerve growth factor are largely limited by its intrinsic disadvantages, such as its short biological half-life, its contribution to pain response, and its inability to cross th...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2023-01-01
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| Series: | Neural Regeneration Research |
| Subjects: | |
| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=7;spage=1584;epage=1590;aulast=Chen |
| _version_ | 1797954710992322560 |
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| author | Qian-Qian Chen Qian-Yan Liu Pan Wang Tian-Mei Qian Xing-Hui Wang Sheng Yi Shi-Ying Li |
| author_facet | Qian-Qian Chen Qian-Yan Liu Pan Wang Tian-Mei Qian Xing-Hui Wang Sheng Yi Shi-Ying Li |
| author_sort | Qian-Qian Chen |
| collection | DOAJ |
| description | Neurotrophic factors, particularly nerve growth factor, enhance neuronal regeneration. However, the in vivo applications of nerve growth factor are largely limited by its intrinsic disadvantages, such as its short biological half-life, its contribution to pain response, and its inability to cross the blood-brain barrier. Considering that let-7 (human miRNA) targets and regulates nerve growth factor, and that let-7 is a core regulator in peripheral nerve regeneration, we evaluated the possibilities of let-7 application in nerve repair. In this study, anti-let-7a was identified as the most suitable let-7 family molecule by analyses of endogenous expression and regulatory relationship, and functional screening. Let-7a antagomir demonstrated biosafety based on the results of in vivo safety assessments and it entered into the main cell types of the sciatic nerve, including Schwann cells, fibroblasts and macrophages. Use of hydrogel effectively achieved controlled, localized, and sustained delivery of let-7a antagomir. Finally, let-7a antagomir was integrated into chitosan conduit to construct a chitosan-hydrogel scaffold tissue-engineered nerve graft, which promoted nerve regeneration and functional recovery in a rat model of sciatic nerve transection. Our study provides an experimental basis for potential in vivo application of let-7a. |
| first_indexed | 2024-04-10T23:22:54Z |
| format | Article |
| id | doaj.art-3cf323ab8015405a89b27f97c3c10173 |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-04-10T23:22:54Z |
| publishDate | 2023-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj.art-3cf323ab8015405a89b27f97c3c101732023-01-12T13:29:30ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742023-01-011871584159010.4103/1673-5374.357914Potential application of let-7a antagomir in injured peripheral nerve regenerationQian-Qian ChenQian-Yan LiuPan WangTian-Mei QianXing-Hui WangSheng YiShi-Ying LiNeurotrophic factors, particularly nerve growth factor, enhance neuronal regeneration. However, the in vivo applications of nerve growth factor are largely limited by its intrinsic disadvantages, such as its short biological half-life, its contribution to pain response, and its inability to cross the blood-brain barrier. Considering that let-7 (human miRNA) targets and regulates nerve growth factor, and that let-7 is a core regulator in peripheral nerve regeneration, we evaluated the possibilities of let-7 application in nerve repair. In this study, anti-let-7a was identified as the most suitable let-7 family molecule by analyses of endogenous expression and regulatory relationship, and functional screening. Let-7a antagomir demonstrated biosafety based on the results of in vivo safety assessments and it entered into the main cell types of the sciatic nerve, including Schwann cells, fibroblasts and macrophages. Use of hydrogel effectively achieved controlled, localized, and sustained delivery of let-7a antagomir. Finally, let-7a antagomir was integrated into chitosan conduit to construct a chitosan-hydrogel scaffold tissue-engineered nerve graft, which promoted nerve regeneration and functional recovery in a rat model of sciatic nerve transection. Our study provides an experimental basis for potential in vivo application of let-7a.http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=7;spage=1584;epage=1590;aulast=Chenchitosan; chitosan-hydrogel scaffold; let-7; let-7a antagomir; mirna; nerve graft; peripheral nerve injury; peripheral nerve regeneration; schwann cells |
| spellingShingle | Qian-Qian Chen Qian-Yan Liu Pan Wang Tian-Mei Qian Xing-Hui Wang Sheng Yi Shi-Ying Li Potential application of let-7a antagomir in injured peripheral nerve regeneration Neural Regeneration Research chitosan; chitosan-hydrogel scaffold; let-7; let-7a antagomir; mirna; nerve graft; peripheral nerve injury; peripheral nerve regeneration; schwann cells |
| title | Potential application of let-7a antagomir in injured peripheral nerve regeneration |
| title_full | Potential application of let-7a antagomir in injured peripheral nerve regeneration |
| title_fullStr | Potential application of let-7a antagomir in injured peripheral nerve regeneration |
| title_full_unstemmed | Potential application of let-7a antagomir in injured peripheral nerve regeneration |
| title_short | Potential application of let-7a antagomir in injured peripheral nerve regeneration |
| title_sort | potential application of let 7a antagomir in injured peripheral nerve regeneration |
| topic | chitosan; chitosan-hydrogel scaffold; let-7; let-7a antagomir; mirna; nerve graft; peripheral nerve injury; peripheral nerve regeneration; schwann cells |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=7;spage=1584;epage=1590;aulast=Chen |
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