2. Academic Validation
  3. Ozone alleviates MSU-induced acute gout pain via upregulating AMPK/GAS6/MerTK/SOCS3 signaling pathway

Ozone alleviates MSU-induced acute gout pain via upregulating AMPK/GAS6/MerTK/SOCS3 signaling pathway

  • J Transl Med. 2023 Dec 8;21(1):890. doi: 10.1186/s12967-023-04769-1.
Wen Fan # 1,  Chong Liu # 1,  Dacai Chen # 2 3,  Chenjie Xu 4,  Xiuting Qi 1,  Ailin Zhang 5,  Xuexian Zhu 1,  Yujie Liu 1,  Lei Wang 1,  Lanxiang Hao 6,  Wen-Tao Liu 7,  Liang Hu 8
Affiliations

Affiliations

  • 1 Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China.
  • 2 The Fourth Affiliated Hospital of Nantong University, Jiangsu, China.
  • 3 Yancheng Ruikang Hospital, Jiangsu, 224000, China.
  • 4 Department of Anesthesiology and Pain, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, Jiangsu, China.
  • 5 Nanjing University of Chinese Medicine Institute of Literature in Chinese Medicine, Jiangsu, 224000, China.
  • 6 The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, Jiangsu, 224005, China. [email protected].
  • 7 Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China. [email protected].
  • 8 Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China. [email protected].
  • # Contributed equally.
PMID: 38066599 DOI: 10.1186/s12967-023-04769-1
Abstract

Background: Gout pain seriously affects the quality of patients' life. There is still no effective treatment. The inflammatory response is the main mechanism of gout. Here, we found that ozone can reduce the inflammatory reaction in the joints of gouty mice and relieve gout pain, and we further explore its protective mechanism.

Methods: MSU was used to establish the gouty mice model. Nociception was assessed by Von Frey hairs. Cell signaling assays were performed by western blotting and immunohistochemistry. The mouse leukemia cells of monocyte macrophage line RAW264.7 were cultured to investigate the effects of ozone administration on macrophage.

Results: Ozone reduced inflammation, relieved gout pain and improved the paw mean intensity and duty cycle of the gouty mice. Ozone increased the phosphorylation of AMP-activated protein kinase (AMPK), induced suppressor of cytokine signaling 3 (SOCS3) expression and inhibited metallopeptidase 9 (MMP9) expression. In vivo, ozone activated AMPK to induce Gas6 release, and upregulated MerTK/SOCS3 signaling pathway to reduce inflammation in mouse macrophage line RAW264.7. Inhibitors of AMPK and MerTK, respectively abolished the analgesic and anti-inflammatory effects of ozone in vivo and in vitro. Gas6 knockout cancelled the protectively effects of ozone on gout pain and the paw mean intensity and duty cycle of gouty mice. Additionally, the level of Gas6 and protein S in plasma of patients with hyperuricemia was significantly higher than that of healthy contrast group.

Conclusion: Ozone reduces inflammation and alleviates gout pain by activating AMPK to up-regulate Gas6/MerTK/SOCS3 signaling pathway.

Keywords

AMPK; Gas 6; MMP9; MerTK; Ozone; SOCS3.

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