2. Academic Validation
  3. Unraveling the molecular complexity: Wtap/Ythdf1 and Lcn2 in novel traumatic brain injury secondary injury mechanisms

Unraveling the molecular complexity: Wtap/Ythdf1 and Lcn2 in novel traumatic brain injury secondary injury mechanisms

  • Cell Biol Toxicol. 2024 Aug 7;40(1):65. doi: 10.1007/s10565-024-09909-x.
Chaobang Ma # 1 2,  Caili Gou # 1,  Shiyu Sun # 1 2,  Junmin Wang 3,  Xin Wei 1,  Fei Xing 1,  Na Xing 1,  Jingjing Yuan 4,  Zhongyu Wang 5 6 7
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, No.1, Jianshe East Road, Erqi District, Zhengzhou, 450052, Henan, China.
  • 2 Henan Province International Joint Laboratory of Pain, Cognition and Emotion, Zhengzhou, 450052, Henan, China.
  • 3 Department of Human Anatomy Basic Medical College of Zhengzhou University, Zhengzhou, 450001, Henan, China.
  • 4 Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, No.1, Jianshe East Road, Erqi District, Zhengzhou, 450052, Henan, China. yjingjing_99@163.com.
  • 5 Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, No.1, Jianshe East Road, Erqi District, Zhengzhou, 450052, Henan, China. wzy781217@163.com.
  • 6 Henan Province International Joint Laboratory of Pain, Cognition and Emotion, Zhengzhou, 450052, Henan, China. wzy781217@163.com.
  • 7 Department of Human Anatomy Basic Medical College of Zhengzhou University, Zhengzhou, 450001, Henan, China. wzy781217@163.com.
  • # Contributed equally.
PMID: 39110292 DOI: 10.1007/s10565-024-09909-x
Abstract

The primary aim of this research was to explore the functions of Wtap and Ythdf1 in regulating neuronal Lipocalin-2 (Lcn2) through m6A modification in traumatic brain injury (TBI). By employing transcriptome Sequencing and enrichment analysis, we identified the Wtap/Ythdf1-mediated Lcn2 m6A modification pathway as crucial in TBI. In our in vitro experiments using primary cortical neurons, knockout of Wtap and Ythdf1 led to the inhibition of Lcn2 m6A modification, resulting in reduced neuronal death and inflammation. Furthermore, overexpression of Lcn2 in cortical neurons induced the activation of reactive astrocytes and M1-like microglial cells, causing neuronal Apoptosis. In vivo experiments confirmed the activation of reactive astrocytes and microglial cells in TBI and importantly demonstrated that Wtap knockdown improved neuroinflammation and functional impairment. These findings underscore the significance of Wtap/Ythdf1-mediated Lcn2 regulation in TBI secondary injury and suggest potential therapeutic implications for combating TBI-induced neuroinflammation and neuronal damage.

Keywords

Lcn2; Traumatic brain injury; Wtap; Ythdf1; m6A modification.

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