2. Academic Validation
  3. Branched-chain aminotransferase 1 promotes Schwann cell migration and proliferation to accelerate facial nerve regeneration through the Twist/FoxC1 and Sox2 pathways

Branched-chain aminotransferase 1 promotes Schwann cell migration and proliferation to accelerate facial nerve regeneration through the Twist/FoxC1 and Sox2 pathways

  • Int J Biol Macromol. 2023 May 19;242(Pt 2):124870. doi: 10.1016/j.ijbiomac.2023.124870.
Zheng Chen 1,  Yinda Tang 1,  Wanchun Zhu 1,  Haopeng Wang 1,  Xiaomin Cai 1,  Yiman Shen 1,  Baimiao Wang 1,  Hua Zhao 2,  Jin Zhu 3,  Shiting Li 4
Affiliations

Affiliations

  • 1 Department of Neurosurgery, XinHua Hospital, Shanghai JiaoTong University School of Medicine, 1665 KongJiang Rd, Shanghai 200092, China; The Cranial Nerve Disease Center of Shanghai JiaoTong University, Shanghai 200092, China.
  • 2 Department of Neurosurgery, XinHua Hospital, Shanghai JiaoTong University School of Medicine, 1665 KongJiang Rd, Shanghai 200092, China; The Cranial Nerve Disease Center of Shanghai JiaoTong University, Shanghai 200092, China. Electronic address: zhaohua@xinhuamed.com.cn.
  • 3 Department of Neurosurgery, XinHua Hospital, Shanghai JiaoTong University School of Medicine, 1665 KongJiang Rd, Shanghai 200092, China; The Cranial Nerve Disease Center of Shanghai JiaoTong University, Shanghai 200092, China. Electronic address: medzhujin@126.com.
  • 4 Department of Neurosurgery, XinHua Hospital, Shanghai JiaoTong University School of Medicine, 1665 KongJiang Rd, Shanghai 200092, China; The Cranial Nerve Disease Center of Shanghai JiaoTong University, Shanghai 200092, China. Electronic address: lishiting@xinhuamed.com.cn.
PMID: 37196723 DOI: 10.1016/j.ijbiomac.2023.124870
Abstract

Facial paralysis caused by injury to the facial nerve is common clinical presentation resulting in significant physical and psychological damage. In addition, due to the lack of understanding about the mechanisms of injury and repair and the lack of effective treatment targets, the clinical treatment outcomes for such patients remain poor. Schwann cells (SCs) have a central role in the regeneration of nerve myelin. In a rat model of facial nerves crush injury, we found that branched-chain aminotransferase 1 (BCAT1) was upregulated after injury. Moreover, it had a positive role in nerve repair. Using intervention methods such as gene knockdown, overexpression, and protein-specific inhibitors, combined with detection methods such as CCK8, Transwell, EdU, and flow cytometry, we demonstrated that BCAT1 significantly enhanced the migration and proliferation of SCs. It affected SC cell migration by regulating the Twist/Foxc1 signal axis and promoted cell proliferation by directly regulating the expression of SOX2. Similarly, animal experiments demonstrated that BCAT1 promotes facial nerve repair, improving nerve function and myelin regeneration by activating both the Twist/Foxc1 and SOX2 axes. In sum, BCAT1 promotes SC migration and proliferation, suggesting its potential as a key molecular target for improving the outcome of facial nerve injury repairs.

Keywords

Branched-chain aminotransferase 1; Dual signal pathway; Facial nerve injury.

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