2. Academic Validation
  3. Polyene phosphatidylcholine ameliorates synovial inflammation: involvement of PTEN elevation and glycolysis suppression

Polyene phosphatidylcholine ameliorates synovial inflammation: involvement of PTEN elevation and glycolysis suppression

  • Mol Biol Rep. 2022 Nov 12. doi: 10.1007/s11033-022-08043-3.
Fenfen Sun # 1 2,  Wenting Hao # 1 3,  Xianran Meng # 1,  Daxiang Xu 1,  Xiangyang Li 1,  Kuiyang Zheng 1,  Yinghua Yu 1,  Dahui Wang 4,  Wei Pan 5
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 2 National Experimental Teaching Demonstration Center of Basic Medicine (Xuzhou Medical University), Xuzhou, Jiangsu, China.
  • 3 Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 4 Liangshan College (Li Shui) China, Lishui University, Lishui, Zhejiang, China. [email protected].
  • 5 Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China. [email protected].
  • # Contributed equally.
PMID: 36370296 DOI: 10.1007/s11033-022-08043-3
Abstract

Background: Synovial inflammation, characterized by the activation of synovial fibroblasts (SFs), is a crucial factor to drive the progression of rheumatoid arthritis (RA). Polyene phosphatidylcholine (PPC), the classic hepatoprotective drug, has been reported to ameliorate arthritis in Animals. However, the molecular mechanism remains poorly understood. METHODS AND RESULTS: Using in vitro primary synovial fibroblast (SFs) culture system, we revealed that Phosphatase and tension homolog deleted on chromosome 10 (PTEN), a tumor suppressor, mediates the anti-inflammatory effect of PPC in lipopolysaccharide (LPS)-stimulated primary SFs. PPC decreased the production of TNF-α and IL-6 production while elevating the level of IL-10 and TGF-β. Furthermore, PPC up-regulated the expression of PTEN, but inhibited the expression of p-AKT (ser473) and PI3K-p85α. Moreover, pre-treatment of SF1670 (the inhibitor of PTEN) or 740Y-P (the agonist of Akt/PI3K pathways) partially abrogated the anti-inflammatory effect of PPC. In addition, PPC could inhibit the expression of GLUT4, a key transporter of glucose that fuels the glycolysis, which is accompanied by the expression downregualtion of glycolytic enzymes PFKFB3 and PKM2. Furthermore, PPC could reduce ROS production and mitochondrial membrane potential in LPS-stimulated SFs and MH7A cell line.

Conclusion: The present study supported that PPC can alleviate synovial inflammation, which involves in the elevation of PTEN and blockage of glycolysis.

Keywords

Glycolysis; PTEN; Polyene phosphatidylcholine; Rheumatoid athritis; Synovial inflammation.

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