A&R: Semaphorin3B 在血清诱导的关节炎模型中起核心作用,在类风湿性关节炎患者中降低

2022-01-21 网络 网络

Sema(phorin)3B表达在关节炎小鼠模型中具有保护作用。在RA患者中,Sema3B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:Sema(phorin)3B 是一种分泌蛋白,属于semaphorin家族,参与不同的生物学过程,如细胞凋亡、血管生成、细胞迁移和侵袭。之前发现Sema(phorin)3B降低类风湿性关节炎 (RA) 成纤维样滑膜细胞 (FLS) 的迁移和侵袭能力,并抑制基质金属蛋白酶 (MMPs) 的表达。在这篇研究中,作者们确定了 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:在关节炎的K/BxN血清转移模型中检查了野生型 (WT) Sema3B缺陷型 (Sema3b-/-)小鼠的临床反应、组织学分析和FLS功能。通过ELISA、蛋白免疫印迹、qPCR RNA测序确定来自小鼠关节和小鼠FLS,以及来自关节痛和RA患者的血清和滑膜组织的蛋白质和mRNA 表达。使用伤口闭合实验测量FLS迁移情况。

     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明显更高。这与炎症介质的表达增加和mFLS的迁移能力有关。重组Sema3B的给药在小鼠模型中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,已确诊的RA患者的滑膜组织和血清中Sema3B的表达显著降低。Sema3B血清水平在后来发展为 RA的关节痛患者中升高,但在未发展为RA的患者中不升高;然而,这些水平在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具有保护作用。在RA患者中,Sema3B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。

 

出处:

Igea, A., Carvalheiro, T., Malvar-Fernández, B., Martinez-Ramos, et al. (2022), Semaphorin3B plays a central role in serum-induced arthritis model and is reduced in patients with rheumatoid arthritis. Arthritis Rheumatol. Accepted Author Manuscript. https://doi.org/10.1002/art.42065

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    2022-08-02 chg121
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    2022-01-23 lmm397
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    2022-01-23 fengyi812
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    2022-01-22 仁术2021

    不错,学习了

    0

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