Neuregulin-1/ErbB4 upregulates acetylcholine receptors via Akt/mTOR/p70S6K: a study in a rat model of obstetric brachial plexus palsy and in vitro
In obstetric brachial plexus palsy (OBPP), the operative time window for nerve reconstruction of the intrinsic muscles of the hand (IMH) is much shorter than that of biceps. The reason is that the atrophy of IMH becomes irreversible more quickly than that of biceps. A previous study confirmed that t...
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| Format: | Article |
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China Science Publishing & Media Ltd.
2022-11-01
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| Series: | Acta Biochimica et Biophysica Sinica |
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| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2022158 |
| _version_ | 1797635311857041408 |
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| author | Qiao Jing Sun Jiayu Chen Liang Li Bo Gu Yudong |
| author_facet | Qiao Jing Sun Jiayu Chen Liang Li Bo Gu Yudong |
| author_sort | Qiao Jing |
| collection | DOAJ |
| description | In obstetric brachial plexus palsy (OBPP), the operative time window for nerve reconstruction of the intrinsic muscles of the hand (IMH) is much shorter than that of biceps. The reason is that the atrophy of IMH becomes irreversible more quickly than that of biceps. A previous study confirmed that the motor endplates of denervated intrinsic muscles of the forepaw (IMF) were destabilized, while those of denervated biceps remained intact. However, the specific molecular mechanism of regulating the self-repair of motor endplates is still unknown. In this study, we use a rat model of OBPP with right C5-C6 rupture plus C7-C8-T1 avulsion and left side as a control. Bilateral IMF and biceps are harvested at 5 weeks postinjury to assess relative protein and mRNA expression. We also use L6 skeletal myoblasts to verify the effects of signaling pathways regulating acetylcholine receptor (AChR) protein synthesis in vitro. The results show that in the OBPP rat model, the protein and mRNA expression levels of NRG-1/ErbB4 and phosphorylation of Akt/mTOR/p70S6K are lower in denervated IMF than in denervated biceps. In L6 myoblasts stimulated with NRG-1, overexpression and knockdown of ErbB4 lead to upregulation and downregulation of AChR subunit protein synthesis and Akt/mTOR/p70S6K phosphorylation, respectively. Inhibition of mTOR abolishes protein synthesis of AChR subunits elevated by NRG-1/ErbB4. Our findings suggest that in the OBPP rat model, lower expression of AChR subunits in the motor endplates of denervated IMF is associated with downregulation of NRG-1/ErbB4 and phosphorylation of Akt/mTOR/p70S6K. NRG-1/ErbB4 can promote protein synthesis of the AChR subunits in L6 myoblasts via phosphorylation of Akt/mTOR/p70S6K. |
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| institution | Directory Open Access Journal |
| issn | 1672-9145 |
| language | English |
| last_indexed | 2024-03-11T12:20:26Z |
| publishDate | 2022-11-01 |
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| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj.art-0bac1310986e4f15ac35e4eff4faf60e2023-11-07T01:02:32ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452022-11-01541648165710.3724/abbs.202215820d259ccNeuregulin-1/ErbB4 upregulates acetylcholine receptors via Akt/mTOR/p70S6K: a study in a rat model of obstetric brachial plexus palsy and in vitroQiao Jing0Sun Jiayu1Chen Liang2Li Bo3Gu Yudong4["Department of Hand Surgery, Huashan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai 200040, China","Key Laboratory of Hand Reconstruction, Ministry of Health, Shanghai 200040, China","Shanghai Key Laboratory of Peripheral Nerve and Microsurgery, Shanghai 200040, China"]["Department of Hand Surgery, Huashan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai 200040, China","Key Laboratory of Hand Reconstruction, Ministry of Health, Shanghai 200040, China","Shanghai Key Laboratory of Peripheral Nerve and Microsurgery, Shanghai 200040, China"]["Department of Hand Surgery, Huashan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai 200040, China","Key Laboratory of Hand Reconstruction, Ministry of Health, Shanghai 200040, China","Shanghai Key Laboratory of Peripheral Nerve and Microsurgery, Shanghai 200040, China"]["Department of Orthopedic Surgery, Yangpu Hospital, Tongji University, Shanghai 200090, China"]["Department of Hand Surgery, Huashan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai 200040, China","Key Laboratory of Hand Reconstruction, Ministry of Health, Shanghai 200040, China","Shanghai Key Laboratory of Peripheral Nerve and Microsurgery, Shanghai 200040, China"]In obstetric brachial plexus palsy (OBPP), the operative time window for nerve reconstruction of the intrinsic muscles of the hand (IMH) is much shorter than that of biceps. The reason is that the atrophy of IMH becomes irreversible more quickly than that of biceps. A previous study confirmed that the motor endplates of denervated intrinsic muscles of the forepaw (IMF) were destabilized, while those of denervated biceps remained intact. However, the specific molecular mechanism of regulating the self-repair of motor endplates is still unknown. In this study, we use a rat model of OBPP with right C5-C6 rupture plus C7-C8-T1 avulsion and left side as a control. Bilateral IMF and biceps are harvested at 5 weeks postinjury to assess relative protein and mRNA expression. We also use L6 skeletal myoblasts to verify the effects of signaling pathways regulating acetylcholine receptor (AChR) protein synthesis in vitro. The results show that in the OBPP rat model, the protein and mRNA expression levels of NRG-1/ErbB4 and phosphorylation of Akt/mTOR/p70S6K are lower in denervated IMF than in denervated biceps. In L6 myoblasts stimulated with NRG-1, overexpression and knockdown of ErbB4 lead to upregulation and downregulation of AChR subunit protein synthesis and Akt/mTOR/p70S6K phosphorylation, respectively. Inhibition of mTOR abolishes protein synthesis of AChR subunits elevated by NRG-1/ErbB4. Our findings suggest that in the OBPP rat model, lower expression of AChR subunits in the motor endplates of denervated IMF is associated with downregulation of NRG-1/ErbB4 and phosphorylation of Akt/mTOR/p70S6K. NRG-1/ErbB4 can promote protein synthesis of the AChR subunits in L6 myoblasts via phosphorylation of Akt/mTOR/p70S6K. https://www.sciengine.com/doi/10.3724/abbs.2022158acetylcholine receptor subunitsdenervationmotor endplatesobstetric brachial plexus palsy |
| spellingShingle | Qiao Jing Sun Jiayu Chen Liang Li Bo Gu Yudong Neuregulin-1/ErbB4 upregulates acetylcholine receptors via Akt/mTOR/p70S6K: a study in a rat model of obstetric brachial plexus palsy and in vitro Acta Biochimica et Biophysica Sinica acetylcholine receptor subunits denervation motor endplates obstetric brachial plexus palsy |
| title | Neuregulin-1/ErbB4 upregulates acetylcholine receptors via Akt/mTOR/p70S6K: a study in a rat model of obstetric brachial plexus palsy and in vitro |
| title_full | Neuregulin-1/ErbB4 upregulates acetylcholine receptors via Akt/mTOR/p70S6K: a study in a rat model of obstetric brachial plexus palsy and in vitro |
| title_fullStr | Neuregulin-1/ErbB4 upregulates acetylcholine receptors via Akt/mTOR/p70S6K: a study in a rat model of obstetric brachial plexus palsy and in vitro |
| title_full_unstemmed | Neuregulin-1/ErbB4 upregulates acetylcholine receptors via Akt/mTOR/p70S6K: a study in a rat model of obstetric brachial plexus palsy and in vitro |
| title_short | Neuregulin-1/ErbB4 upregulates acetylcholine receptors via Akt/mTOR/p70S6K: a study in a rat model of obstetric brachial plexus palsy and in vitro |
| title_sort | neuregulin 1 erbb4 upregulates acetylcholine receptors via akt mtor p70s6k a study in a rat model of obstetric brachial plexus palsy and in vitro |
| topic | acetylcholine receptor subunits denervation motor endplates obstetric brachial plexus palsy |
| url | https://www.sciengine.com/doi/10.3724/abbs.2022158 |
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