2. Academic Validation
  3. TGF-β1 Protects Trauma-injured Murine Cortical Neurons by Upregulating L-type Calcium Channel Cav1.2 via the p38 Pathway

TGF-β1 Protects Trauma-injured Murine Cortical Neurons by Upregulating L-type Calcium Channel Cav1.2 via the p38 Pathway

  • Neuroscience. 2022 Jun 1;492:47-57. doi: 10.1016/j.neuroscience.2022.04.010.
Yanlei Li 1,  Weiqiang Chen 2,  Huixiong Deng 3,  Tian Li 4,  Zhenning Liu 5,  Xueer Liu 6,  Zelin Zhang 7,  Xiaoxuan Chen 8,  Jiangtao Sheng 9,  Kangsheng Li 10
Affiliations

Affiliations

  • 1 Department of Microbiology and Immunology, Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, China. Electronic address: 16ylli3@stu.edu.cn.
  • 2 Department of Neurosurgery, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China. Electronic address: wqchen@stu.edu.cn.
  • 3 Department of Microbiology and Immunology, Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, China. Electronic address: hxdeng@stu.edu.cn.
  • 4 Department of Microbiology and Immunology, Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, China. Electronic address: 16tli1@stu.edu.cn.
  • 5 Department of Laboratory, Guangzhou Chest Hospital, China. Electronic address: zhenning_liu@163.com.
  • 6 Department of Microbiology and Immunology, Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, China. Electronic address: xueerau@163.com.
  • 7 Department of Microbiology and Immunology, Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, China. Electronic address: 21zlzhang@stu.edu.cn.
  • 8 Department of Microbiology and Immunology, Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, China. Electronic address: chen.x.x.85@163.com.
  • 9 Department of Microbiology and Immunology, Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, China. Electronic address: jtsheng@stu.edu.cn.
  • 10 Department of Microbiology and Immunology, Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, China. Electronic address: ksli@stu.edu.cn.
PMID: 35460836 DOI: 10.1016/j.neuroscience.2022.04.010
Abstract

Traumatic brain injury (TBI) is a leading cause of disability and death in adolescents, and there is a lack of effective methods of treatment. The neuroprotective effects exerted by TGF-β1 can ameliorate a range of neuronal lesions in multiple central nervous system diseases. In this study, we used an in-vitro TBI model of mechanical injury on murine primary cortical neurons and the neuro-2a cell line to investigate the neuroprotective role played by TGF-β1 in cortical neurons in TBI. Our results showed that TGF-β1 significantly increased neuronal viability and inhibited Apoptosis for 24 h after trauma. The expression of CAv1.2, an L-type calcium channel (LTCC) isoform, decreased significantly after trauma injury, and this change was reversed by TGF-β1. Nimodipine, a classic LTCC blocker, abolished the protective effect of TGF-β1 on trauma-induced neuronal Apoptosis. The knockdown of CAv1.2 in differentiated neuro-2a cells significantly inhibited the anti-apoptosis effect of TGF-β1 exerted on injured neuro-2a cells. Moreover, TGF-β1 rescued and enhanced the trauma-suppressed neuro-2a intracellular CA2+ concentration, while the effect of TGF-β1 was partially inhibited by nimodipine. TGF-β1 significantly upregulated the expression of CAv1.2 by activating the p38 MAPK pathway and by inhibiting trauma-induced neuronal Apoptosis. In conclusion, TGF-β1 increased trauma-injured murine cortical neuronal activity and inhibited Apoptosis by upregulating Cav1.2 channels via activating the p38 MAPK pathway. Therefore, the TGF-β1/p38 MAPK/CAv 1.2 pathway has the potential to be used as a novel therapeutic target for TBI.

Keywords

L-type calcium channel; cortical neuron; neuro-2a; p38-mitogen-activated protein kinase; transforming growth factor-β1; traumatic brain injury.

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