Investigating the role of IL-6 in the pathogenesis of systemic lupus erythematosus: Insights from bone marrow mesenchymal stem cells.

IF 1.9 4区 医学 Q3 RHEUMATOLOGY Lupus Pub Date : 2025-03-01 Epub Date: 2025-01-30 DOI:10.1177/09612033251317783
Zhiwen Zhang, Silang Zhu, Qian Li, Shanshan Wei, Li Yin, Junhao Zhu, Shan Yang, Wenjing Zhang, Kuan Lai
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Abstract

BackgroundSystemic lupus erythematosus is a common autoimmune disease. Studies have suggested that defective stem cells could be involved in the pathogenesis of systemic lupus erythematosus, which leads to changes in the function of immune cells. By observing the cell morphology, autophagy, and senescence of bone marrow mesenchymal stem cells (BMSCs) from lupus mice and normal controls, this study investigated the role of IL-6 in autophagy and senescence of BMSCs and explored relevant mechanisms.MethodFemale MRL/lpr and C57 mice with similar weights and sizes at 20-22 weeks old were selected. BMSCs were isolated using the whole bone marrow adherent method. Quantitative real-time polymerase chain reaction, β-galactosidase staining, western blotting, and ELISA were used to detect autophagy and senescence.ResultCompared with BMSCs from normal mice, BMSCs from lupus mice exhibited low autophagy and premature senescence with a senescence-associated secretory phenotype. The addition of exogenous IL-6 increased the protein levels of p-STAT3 and Bcl-2, and in the IL-6-treated group, the premature senescence of cells increased and autophagy decreased.ConclusionThe biological functions of BMSCs from MRL/lpr lupus mice were impaired. IL-6 prevents autophagy and subsequently promotes the senescence of BMSCs by activating the IL-6/STAT3 pathway.

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研究IL-6在系统性红斑狼疮发病机制中的作用:来自骨髓间充质干细胞的见解。
背景:系统性红斑狼疮是一种常见的自身免疫性疾病。研究表明,有缺陷的干细胞可能参与系统性红斑狼疮的发病机制,导致免疫细胞功能的改变。本研究通过观察狼疮小鼠和正常对照骨髓间充质干细胞(BMSCs)的细胞形态、自噬和衰老情况,探讨IL-6在骨髓间充质干细胞自噬和衰老中的作用,并探讨相关机制。方法:选取20 ~ 22周龄体重、体型相近的MRL/lpr、C57雌性小鼠。采用全骨髓贴壁法分离骨髓间充质干细胞。采用实时定量聚合酶链反应、β-半乳糖苷酶染色、western blotting、ELISA检测细胞自噬和衰老情况。结果:与正常小鼠骨髓间充质干细胞相比,狼疮小鼠骨髓间充质干细胞表现出低自噬和早衰老的特点,并伴有衰老相关的分泌表型。外源IL-6的加入使p-STAT3和Bcl-2蛋白水平升高,IL-6处理组细胞早衰加剧,自噬减少。结论:MRL/lpr狼疮小鼠骨髓间充质干细胞生物学功能受损。IL-6通过激活IL-6/STAT3通路阻止骨髓间充质干细胞自噬,进而促进其衰老。
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来源期刊
Lupus
Lupus 医学-风湿病学
CiteScore
4.20
自引率
11.50%
发文量
225
审稿时长
1 months
期刊介绍: The only fully peer reviewed international journal devoted exclusively to lupus (and related disease) research. Lupus includes the most promising new clinical and laboratory-based studies from leading specialists in all lupus-related disciplines. Invaluable reading, with extended coverage, lupus-related disciplines include: Rheumatology, Dermatology, Immunology, Obstetrics, Psychiatry and Cardiovascular Research…
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