Precise Lipidomics Decipher Circulating Ceramide and Sphingomyelin Cycle Associated with the Progression of Rheumatoid Arthritis,Journal of Proteome Research

当前位置： X-MOL 学术 › J. Proteome Res. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Precise Lipidomics Decipher Circulating Ceramide and Sphingomyelin Cycle Associated with the Progression of Rheumatoid Arthritis
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2023-10-26 , DOI: 10.1021/acs.jproteome.3c00574
Hemi Luan ₁ , Shuailong Chen ₂ , Longshan Zhao ₂ , Shijia Liu ₃ , Tiangang Luan _{1,

4,

5}

Affiliation

Rheumatoid arthritis (RA) is a long-term autoimmune condition that causes joint and surrounding tissue inflammation. Lipid mediators are involved in inflammation and deterioration of the joints. Despite attempts to discover effective drug targets to intervene with lipid metabolism in the disease, progress has been limited. In this study, precise lipidomic technology was employed to quantify a broad range of serum ceramides and sphingomyelin (SM) in a large cohort, revealing an association between the accumulation of circulating ceramides and disturbed ceramide/SM cycles during the progression of RA. In our investigation, we discovered that eight ceramides exhibited a positive correlation with the activity of RA, thereby enhancing the accuracy of RA diagnosis, particularly in patients with serum antibody-negative RA. Furthermore, the enzyme SM phosphodiesterase 3 (SMPD3) was found to disrupt the circulating SM cycle and accelerate the progression of RA. The activity of SMPD3 can be inhibited by methotrexate, resulting in decreased metabolic conversion of SM to ceramide. These findings suggest that targeting the SM cycle may provide a new therapeutic option for RA.

中文翻译：

精确的脂质组学破译与类风湿关节炎进展相关的循环神经酰胺和鞘磷脂循环

类风湿性关节炎（RA）是一种长期自身免疫性疾病，会导致关节和周围组织炎症。脂质介质参与炎症和关节恶化。尽管尝试发现有效的药物靶点来干预该疾病中的脂质代谢，但进展仍然有限。在这项研究中，采用精确的脂质组学技术对大型队列中的各种血清神经酰胺和鞘磷脂 (SM) 进行定量，揭示了 RA 进展过程中循环神经酰胺的积累与扰乱的神经酰胺/SM 循环之间的关联。在我们的研究中，我们发现八种神经酰胺与 RA 活性呈正相关，从而提高了 RA 诊断的准确性，特别是对于血清抗体阴性 RA 患者。此外，还发现 SM 磷酸二酯酶 3 (SMPD3) 会破坏 SM 循环并加速 RA 的进展。 SMPD3 的活性可被甲氨蝶呤抑制，导致 SM 向神经酰胺的代谢转化减少。这些发现表明，针对 SM 周期可能为 RA 提供新的治疗选择。

更新日期：2023-10-26

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南