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DHI Increases the Proliferation and Migration of Schwann Cells Through the PI3K/AKT Pathway and the Expression of CXCL12 and GDNF to Promote Facial Nerve Function Repair

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Abstract

The facial nerve is one of the vulnerable nerves in otolaryngology. Repair and recovery of facial nerve injury have a high priority in clinical practice. The proliferation and migration of Schwann cells are considered of great significance in the process of nerve injury repair. Danhong injection (DHI), as a common drug for cardiovascular and cerebrovascular diseases, has been fully certified in neuroprotection research, but its role in facial nerve injury is still not clear. Our study found that DHI can promote the proliferation and migration of RSC96 cells, a Schwann cell line, and this effect is related to the activation of the PI3K/AKT pathway. LY294002, an inhibitor of PI3K, inhibits the proliferation and migration of RSC96 cells. Further studies have found that DHI can also promote the expression of CXCL12 and GDNF at gene and protein levels, and CXCL12 is, while GDNF is not, PI3K/AKT pathway-dependent. Animal experiments also confirmed that DHI could promote CXCL12 and GDNF expression and promote facial nerve function recovery and myelin regeneration. In conclusion, our in vitro and in vivo experiments demonstrated that DHI could promote the proliferation and migration of Schwann cells through the PI3K/AKT pathway and increase the expression of CXCL12 and GDNF to promote facial nerve function repair.

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Data Availability

The data presented in this study are available on request from the corresponding author.

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Acknowledgements

Thanks to the support of the National Natural Science Foundation of China (No. 82071069) and the technical platform provided by the Institute of otology.

Funding

We thank the support from the National Natural Science Foundation of China (No. 82071069).

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Author notes

  1. De-kun Gao and Lian-hua Sun have contributed equally to this work.

Authors and Affiliations

  1. Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    De-kun Gao, Lian-hua Sun, Xia-yu Sun, Jun Yang & Jing-chun He

  2. Shanghai Jiaotong University School of Medicine Ear Institute, Shanghai, China

    De-kun Gao, Lian-hua Sun, Xia-yu Sun, Jun Yang & Jing-chun He

  3. Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China

    De-kun Gao, Lian-hua Sun, Xia-yu Sun, Jun Yang & Jing-chun He

Authors
  1. De-kun Gao
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  2. Lian-hua Sun
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  3. Xia-yu Sun
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  4. Jun Yang
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Contributions

DG and JH conceived the idea and wrote the manuscript. DG and LS performed the facial nerve injury model, drug administration, Western blot analysis, and immunofluorescence staining experiments. XS performed ELISA and RT-qPCR experiments. JY and JH reviewed and edited the final manuscript.

Corresponding authors

Correspondence to Jun Yang or Jing-chun He.

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Gao, Dk., Sun, Lh., Sun, Xy. et al. DHI Increases the Proliferation and Migration of Schwann Cells Through the PI3K/AKT Pathway and the Expression of CXCL12 and GDNF to Promote Facial Nerve Function Repair. Neurochem Res 47, 1329–1340 (2022). https://doi.org/10.1007/s11064-022-03532-0

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