2. Academic Validation
  3. Thrombopoietin Mitigates Neuronal Death by Enhancing Mitophagy and Suppressing NLRP3 Inflammasome Activation Under Oxygen-Glucose Deprivation Conditions

Thrombopoietin Mitigates Neuronal Death by Enhancing Mitophagy and Suppressing NLRP3 Inflammasome Activation Under Oxygen-Glucose Deprivation Conditions

  • Am J Physiol Cell Physiol. 2025 Aug 20. doi: 10.1152/ajpcell.00847.2024.
Liang Li 1 2,  Yu Zhang 3,  Junyan Zhong 4,  Huimin Kong 5,  Yong Liu 1 6,  Hui Chen 7 2,  Xiaoyi Fang 8,  Zhiyuan Zhong 1,  Hongman Xue 1,  Mo Yang 6,  Chun Chen 1
Affiliations

Affiliations

  • 1 Pediatric Hematology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affiliated Hospital of Sun Yat-Sen University, 518107, Shenzhen, Guangdong, China.
  • 2 Shenzhen Key Laboratory of Chinese Medicine Active Substance Screening and Translational Research, Shenzhen, 518107, Guangdong, China.
  • 3 Department of Dermato-Venereology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shen zhen, Guangdong, China.
  • 4 Emergency Department, Shenzhen maternity&Child Healthcare Hospital affiliated to Southern Medical University, Shenzhen, 518028, Guangdong, China.
  • 5 Transfusion Department, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China.
  • 6 Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107, Guangdong, China.
  • 7 Department of Pharmacy, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China.
  • 8 Department of Neonatology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107, Guangdong, China.
PMID: 40833847 DOI: 10.1152/ajpcell.00847.2024
Abstract

Thrombopoietin (TPO), a principal hematopoietic cytokine, regulates the development and proliferation of megakaryocytes and platelets. Our previous research demonstrated TPO's neuroprotective role against hypoxic-ischemic brain injury in rats. Yet, the underlying mechanisms remain unclear. This study reveals that A20 (Tumor necrosis factor alpha-induced protein 3, Tnfaip3) significantly contributes to TPO's neuroprotective effect by enhancing Mitophagy in neurons. TPO reduces cell death under oxygen-glucose deprivation (OGD) conditions. Mechanistically, TPO induces the TNF-α and NF-κB signaling pathways to increase A20 expression, thereby promoting Mitophagy, diminishing ROS production, and stabilizing mitochondrial membrane potential (MMP). A20 maintains mitochondrial dynamics and mitigates OGD-induced excessive mitochondrial fission. Furthermore, A20 suppresses NLRP3 inflammasome activation by enhancing Mitophagy. This study elucidates a novel mechanism of TPO's neuroprotection, distinct from its hematological effects, supporting its potential therapeutic application in treating neurological injuries.

Keywords

Mitophagy; NLR Family Pyrin Domain Containing 3; Neuroprotection; Thrombopoietin; Tumor Necrosis Factor Alpha-Induced Protein 3.

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