Sequential expression of miR-221-3p and miR-338-3p in Schwann cells as a therapeutic strategy to promote nerve regeneration and functional recovery
The functional properties of endogenous Schwann cells (SCs) during nerve repair are dynamic. Optimizing the functional properties of SCs at different stages of nerve repair may have therapeutic benefit in improving the repair of damaged nerves. Previous studies showed that miR-221-3p promotes the pr...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Medknow Publications
2023-01-01
|
| Series: | Neural Regeneration Research |
| Subjects: | |
| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=3;spage=671;epage=682;aulast=Wen |
| _version_ | 1798037463750410240 |
|---|---|
| author | Li-Li Wen Tian-Hao Yu Yi-Zhan Ma Xiao-Yan Mao Tian-Rang Ao Rabia Javed Hirotomo Ten Akira Matsuno Qiang Ao |
| author_facet | Li-Li Wen Tian-Hao Yu Yi-Zhan Ma Xiao-Yan Mao Tian-Rang Ao Rabia Javed Hirotomo Ten Akira Matsuno Qiang Ao |
| author_sort | Li-Li Wen |
| collection | DOAJ |
| description | The functional properties of endogenous Schwann cells (SCs) during nerve repair are dynamic. Optimizing the functional properties of SCs at different stages of nerve repair may have therapeutic benefit in improving the repair of damaged nerves. Previous studies showed that miR-221-3p promotes the proliferation and migration of SCs, and miR-338-3p promotes the myelination of SCs. In this study, we established rat models of sciatic nerve injury by bridging the transected sciatic nerve with a silicone tube. We injected a miR-221 lentiviral vector system together with a doxycycline-inducible Tet-On miR-338 lentiviral vector system into the cavity of nerve conduits of nerve stumps to sequentially regulate the biological function of endogenous SCs at different stages of nerve regeneration. We found that the biological function of SCs was sequentially regulated, the diameter and density of myelinated axons were increased, the expression levels of NF200 and myelin basic protein were increased, and the function of injured peripheral nerve was improved using this system. miRNA Target Prediction Database prediction, Nanopore whole transcriptome sequencing, quantitative PCR, and dual luciferase reporter gene assay results predicted and verified Cdkn1b and Nrp1 as target genes of miR-221-3p and miR-338-3p, respectively, and their regulatory effects on SCs were confirmed in vitro. In conclusion, here we established a new method to enhance nerve regeneration through sequential regulation of biological functions of endogenous SCs, which establishes a new concept and model for the treatment of peripheral nerve injury. The findings from this study will provide direct guiding significance for clinical treatment of sciatic nerve injury. |
| first_indexed | 2024-04-11T21:26:53Z |
| format | Article |
| id | doaj.art-8acbd2ea5c1b41a0af4fdaaa80f7be00 |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-04-11T21:26:53Z |
| publishDate | 2023-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj.art-8acbd2ea5c1b41a0af4fdaaa80f7be002022-12-22T04:02:22ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742023-01-0118367168210.4103/1673-5374.350214Sequential expression of miR-221-3p and miR-338-3p in Schwann cells as a therapeutic strategy to promote nerve regeneration and functional recoveryLi-Li WenTian-Hao YuYi-Zhan MaXiao-Yan MaoTian-Rang AoRabia JavedHirotomo TenAkira MatsunoQiang AoThe functional properties of endogenous Schwann cells (SCs) during nerve repair are dynamic. Optimizing the functional properties of SCs at different stages of nerve repair may have therapeutic benefit in improving the repair of damaged nerves. Previous studies showed that miR-221-3p promotes the proliferation and migration of SCs, and miR-338-3p promotes the myelination of SCs. In this study, we established rat models of sciatic nerve injury by bridging the transected sciatic nerve with a silicone tube. We injected a miR-221 lentiviral vector system together with a doxycycline-inducible Tet-On miR-338 lentiviral vector system into the cavity of nerve conduits of nerve stumps to sequentially regulate the biological function of endogenous SCs at different stages of nerve regeneration. We found that the biological function of SCs was sequentially regulated, the diameter and density of myelinated axons were increased, the expression levels of NF200 and myelin basic protein were increased, and the function of injured peripheral nerve was improved using this system. miRNA Target Prediction Database prediction, Nanopore whole transcriptome sequencing, quantitative PCR, and dual luciferase reporter gene assay results predicted and verified Cdkn1b and Nrp1 as target genes of miR-221-3p and miR-338-3p, respectively, and their regulatory effects on SCs were confirmed in vitro. In conclusion, here we established a new method to enhance nerve regeneration through sequential regulation of biological functions of endogenous SCs, which establishes a new concept and model for the treatment of peripheral nerve injury. The findings from this study will provide direct guiding significance for clinical treatment of sciatic nerve injury.http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=3;spage=671;epage=682;aulast=Wencdkn1b; mir-221; mir-338; mirna; nerve regeneration; nrp1; peripheral nerve injury; regulation; schwann cells; sequential expression |
| spellingShingle | Li-Li Wen Tian-Hao Yu Yi-Zhan Ma Xiao-Yan Mao Tian-Rang Ao Rabia Javed Hirotomo Ten Akira Matsuno Qiang Ao Sequential expression of miR-221-3p and miR-338-3p in Schwann cells as a therapeutic strategy to promote nerve regeneration and functional recovery Neural Regeneration Research cdkn1b; mir-221; mir-338; mirna; nerve regeneration; nrp1; peripheral nerve injury; regulation; schwann cells; sequential expression |
| title | Sequential expression of miR-221-3p and miR-338-3p in Schwann cells as a therapeutic strategy to promote nerve regeneration and functional recovery |
| title_full | Sequential expression of miR-221-3p and miR-338-3p in Schwann cells as a therapeutic strategy to promote nerve regeneration and functional recovery |
| title_fullStr | Sequential expression of miR-221-3p and miR-338-3p in Schwann cells as a therapeutic strategy to promote nerve regeneration and functional recovery |
| title_full_unstemmed | Sequential expression of miR-221-3p and miR-338-3p in Schwann cells as a therapeutic strategy to promote nerve regeneration and functional recovery |
| title_short | Sequential expression of miR-221-3p and miR-338-3p in Schwann cells as a therapeutic strategy to promote nerve regeneration and functional recovery |
| title_sort | sequential expression of mir 221 3p and mir 338 3p in schwann cells as a therapeutic strategy to promote nerve regeneration and functional recovery |
| topic | cdkn1b; mir-221; mir-338; mirna; nerve regeneration; nrp1; peripheral nerve injury; regulation; schwann cells; sequential expression |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=3;spage=671;epage=682;aulast=Wen |
| work_keys_str_mv | AT liliwen sequentialexpressionofmir2213pandmir3383pinschwanncellsasatherapeuticstrategytopromotenerveregenerationandfunctionalrecovery AT tianhaoyu sequentialexpressionofmir2213pandmir3383pinschwanncellsasatherapeuticstrategytopromotenerveregenerationandfunctionalrecovery AT yizhanma sequentialexpressionofmir2213pandmir3383pinschwanncellsasatherapeuticstrategytopromotenerveregenerationandfunctionalrecovery AT xiaoyanmao sequentialexpressionofmir2213pandmir3383pinschwanncellsasatherapeuticstrategytopromotenerveregenerationandfunctionalrecovery AT tianrangao sequentialexpressionofmir2213pandmir3383pinschwanncellsasatherapeuticstrategytopromotenerveregenerationandfunctionalrecovery AT rabiajaved sequentialexpressionofmir2213pandmir3383pinschwanncellsasatherapeuticstrategytopromotenerveregenerationandfunctionalrecovery AT hirotomoten sequentialexpressionofmir2213pandmir3383pinschwanncellsasatherapeuticstrategytopromotenerveregenerationandfunctionalrecovery AT akiramatsuno sequentialexpressionofmir2213pandmir3383pinschwanncellsasatherapeuticstrategytopromotenerveregenerationandfunctionalrecovery AT qiangao sequentialexpressionofmir2213pandmir3383pinschwanncellsasatherapeuticstrategytopromotenerveregenerationandfunctionalrecovery |