A&R:Semaphorin 3B在血清诱导的关节炎模型中的中心作用和在类风湿关节炎患者的水平降低

2022-06-13 MedSci原创 MedSci原创

信号素3B (Sema3B)表达在关节炎小鼠模型中起保护作用。在RA患者中,血清中Sema3B的表达水平取决于疾病阶段,表明在疾病发作和进展中具有不同的调节作用。

目的:信号素3B (Sema3B)是一种分泌蛋白,属于信号素家族,参与不同的生物过程Sema3B能降低类风湿性关节炎(RA)中成纤维细胞样滑膜细胞(FLS)的迁移和侵袭能力,并抑制基质金属蛋白酶的表达。该团队进行这项研究以探究Sema3B 在关节炎小鼠模型中的作用及其在RA患者中的表达。

方法:K/BxN关节炎血清转移模型中,在野生型(WT)Sema3B-/-小鼠中检查临床反应、组织学特征和FLS功能。使用酶联免疫吸附测定、免疫印迹、定量聚合酶链反应和 RNA测序测定小鼠关节和小鼠FLS以及关节痛患者和RA患者的血清和滑膜组织中Sema3B的蛋白质和信使RNA表达。使用伤痕闭合测定法确定FLS迁移。

结果:WT小鼠相比,Sema3B-/-小鼠血清诱导的关节炎的临床严重程度显著更高。这与炎症介质的表达增加和小鼠FLS的迁移能力增加有关。重组小鼠Sema3B的给药降低了血清诱导关节炎的临床严重程度和炎症介质的表达。与关节痛患者相比,RA患者的滑膜组织和血清中Sema3B的表达显著降低。关节痛后来发展为RA的患者血清Sema3B水平升高,未发展为RA的患者血清Sema3B水平不升高;然而,Sema3B水平在RA发展后1年和2年急剧下降。

结论Sema3B表达在关节炎小鼠模型中起保护作用。在RA患者中,血清中Sema3B的表达水平取决于疾病阶段,表明在疾病发作和进展中具有不同的调节作用。施用Sema3B可能是一种新的 RA 治疗方法。

出处:Igea, A., Carvalheiro, T., Malvar-Fernández, B., et al. (2022), Central Role of Semaphorin 3B in a Serum-Induced Arthritis Model and Reduced Levels in Patients With Rheumatoid Arthritis. Arthritis Rheumatol, 74: 972-983. https://doi.org/10.1002/art.42065

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    2022-09-07 chg121
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    2022-06-15 lmm397
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    2022-06-15 fengyi812
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