Electroacupuncture-Regulated miR-34a-3p/PDCD6 Axis Promotes Post-Spinal Cord Injury Recovery in Both In Vitro and In Vivo Settings
Electroacupuncture (EA) could enhance neuroregeneration and posttraumatic conditions; however, the underlying regulatory mechanisms remain ambiguous. PDCD6 (programmed cell death 6) is an established proapoptotic regulator which is responsible for motoneuronal death. However, its potential regulator...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2022/9329494 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832563308925812736 |
|---|---|
| author | Lili Ma Lizhong Ma Yu Yang Ting Chen Limin Wang Qilong Deng |
| author_facet | Lili Ma Lizhong Ma Yu Yang Ting Chen Limin Wang Qilong Deng |
| author_sort | Lili Ma |
| collection | DOAJ |
| description | Electroacupuncture (EA) could enhance neuroregeneration and posttraumatic conditions; however, the underlying regulatory mechanisms remain ambiguous. PDCD6 (programmed cell death 6) is an established proapoptotic regulator which is responsible for motoneuronal death. However, its potential regulatory role in post-spinal cord injury (SCI) regeneration has remained largely unknown. Further investigations are warranted to clarify the involvement of PDCD6 post-SCI recovery and the underlying mechanisms. In our study, based on bioinformatics prediction, we found that miR-34a-3p might be an upstream regulator miRNA for PDCD6, which was subsequently validated through combined utilization of the qRT-PCR, western blot, and dual-luciferase reporter system. Our in vitro results showed that miR-34a-3p might promote the in vitro differentiation of neural stem cell (NSC) through suppressing PDCD6 and regulating other important neural markers such as fibroblast growth factor receptor 1 (FGFR1), MAP1/2 (MAP kinase kinases 1/2), myelin basic protein (MBP), βIII-tubulin Class III β-tubulin (βIII tubulin), and glial fibrillary acidic protein (GFAP). Notably, in the post-SCI rat model, exogenous miR-34a-3p agomir obviously inhibited the expression of PDCD6 at the protein level and promoted neuronal proliferation, motoneurons regeneration, and axonal myelination. The restorations at cellular level might contribute to the improved hindlimbs functions of post-SCI rats, which was manifested by the Basso-Beattie-Bresnahan (BBB) locomotor test. The impact of miR-34a-3p was further promoted by EA treatment in vivo. Conclusively, this paper argues that a miR-34a-3p/PDCD6 axis might be a candidate therapeutic target for treating SCI and that the therapeutic effect of EA is driven through this pathway. |
| format | Article |
| id | doaj-art-a9831d9428bf4ac280595798e84c2218 |
| institution | Kabale University |
| issn | 2314-7156 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-a9831d9428bf4ac280595798e84c22182025-02-03T01:20:35ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/9329494Electroacupuncture-Regulated miR-34a-3p/PDCD6 Axis Promotes Post-Spinal Cord Injury Recovery in Both In Vitro and In Vivo SettingsLili Ma0Lizhong Ma1Yu Yang2Ting Chen3Limin Wang4Qilong Deng5Department of Infectious MedicineRehabilitation Medical CenterDepartment of Orthopedic SurgeryDepartment of DermatologyDepartment of Internal NeurologyRehabilitation Medical CenterElectroacupuncture (EA) could enhance neuroregeneration and posttraumatic conditions; however, the underlying regulatory mechanisms remain ambiguous. PDCD6 (programmed cell death 6) is an established proapoptotic regulator which is responsible for motoneuronal death. However, its potential regulatory role in post-spinal cord injury (SCI) regeneration has remained largely unknown. Further investigations are warranted to clarify the involvement of PDCD6 post-SCI recovery and the underlying mechanisms. In our study, based on bioinformatics prediction, we found that miR-34a-3p might be an upstream regulator miRNA for PDCD6, which was subsequently validated through combined utilization of the qRT-PCR, western blot, and dual-luciferase reporter system. Our in vitro results showed that miR-34a-3p might promote the in vitro differentiation of neural stem cell (NSC) through suppressing PDCD6 and regulating other important neural markers such as fibroblast growth factor receptor 1 (FGFR1), MAP1/2 (MAP kinase kinases 1/2), myelin basic protein (MBP), βIII-tubulin Class III β-tubulin (βIII tubulin), and glial fibrillary acidic protein (GFAP). Notably, in the post-SCI rat model, exogenous miR-34a-3p agomir obviously inhibited the expression of PDCD6 at the protein level and promoted neuronal proliferation, motoneurons regeneration, and axonal myelination. The restorations at cellular level might contribute to the improved hindlimbs functions of post-SCI rats, which was manifested by the Basso-Beattie-Bresnahan (BBB) locomotor test. The impact of miR-34a-3p was further promoted by EA treatment in vivo. Conclusively, this paper argues that a miR-34a-3p/PDCD6 axis might be a candidate therapeutic target for treating SCI and that the therapeutic effect of EA is driven through this pathway.http://dx.doi.org/10.1155/2022/9329494 |
| spellingShingle | Lili Ma Lizhong Ma Yu Yang Ting Chen Limin Wang Qilong Deng Electroacupuncture-Regulated miR-34a-3p/PDCD6 Axis Promotes Post-Spinal Cord Injury Recovery in Both In Vitro and In Vivo Settings Journal of Immunology Research |
| title | Electroacupuncture-Regulated miR-34a-3p/PDCD6 Axis Promotes Post-Spinal Cord Injury Recovery in Both In Vitro and In Vivo Settings |
| title_full | Electroacupuncture-Regulated miR-34a-3p/PDCD6 Axis Promotes Post-Spinal Cord Injury Recovery in Both In Vitro and In Vivo Settings |
| title_fullStr | Electroacupuncture-Regulated miR-34a-3p/PDCD6 Axis Promotes Post-Spinal Cord Injury Recovery in Both In Vitro and In Vivo Settings |
| title_full_unstemmed | Electroacupuncture-Regulated miR-34a-3p/PDCD6 Axis Promotes Post-Spinal Cord Injury Recovery in Both In Vitro and In Vivo Settings |
| title_short | Electroacupuncture-Regulated miR-34a-3p/PDCD6 Axis Promotes Post-Spinal Cord Injury Recovery in Both In Vitro and In Vivo Settings |
| title_sort | electroacupuncture regulated mir 34a 3p pdcd6 axis promotes post spinal cord injury recovery in both in vitro and in vivo settings |
| url | http://dx.doi.org/10.1155/2022/9329494 |
| work_keys_str_mv | AT lilima electroacupunctureregulatedmir34a3ppdcd6axispromotespostspinalcordinjuryrecoveryinbothinvitroandinvivosettings AT lizhongma electroacupunctureregulatedmir34a3ppdcd6axispromotespostspinalcordinjuryrecoveryinbothinvitroandinvivosettings AT yuyang electroacupunctureregulatedmir34a3ppdcd6axispromotespostspinalcordinjuryrecoveryinbothinvitroandinvivosettings AT tingchen electroacupunctureregulatedmir34a3ppdcd6axispromotespostspinalcordinjuryrecoveryinbothinvitroandinvivosettings AT liminwang electroacupunctureregulatedmir34a3ppdcd6axispromotespostspinalcordinjuryrecoveryinbothinvitroandinvivosettings AT qilongdeng electroacupunctureregulatedmir34a3ppdcd6axispromotespostspinalcordinjuryrecoveryinbothinvitroandinvivosettings |