J Autoimmun :SB431542 通过调节B细胞和抑制TLR9/TGFβ1/PDGFB信号传导来缓解狼疮性肾炎

2022-09-02 MedSci原创 MedSci原创

该研究表明,SB431542在NZB/W小鼠中抑制蛋白尿并改善组织学损伤。SB431542 通过调节小鼠 B 细胞和 TLR9/TGFβ1/PDGFB 通路减轻 狼疮性肾炎(LN)。

狼疮性肾炎(LN)是系统性红斑狼疮(SLE)患者发病和死亡的最常见原因。目前,LN免疫抑制治疗并不理想,并且会引起明显的副作用。SB431542是一种选择性强效的TGFβ/Activin/NODAL通路抑制剂。来自吉林大学的团队研究了SB431542 治疗对LN的影响并讨论了潜在的机制。

SB431542保护易患狼疮的NZB/W小鼠的肾功能。SB431542减弱抗dsDNA抗体的产生并改善易患狼疮的NZB/W小鼠肾脏的组织学损伤比较转录谱分析显示,SB431542靶向LN的分子/细胞特征。与对照组相比,SB431542组中有586个差异表达基因(247个下调基因)。基因本体论(GO)分析显著识别了与B细胞激活相关的术语发现下调基因主要富集在B细胞活化、B细胞增殖、B细胞分化和B细胞受体信号转导的生物学过程中。京都基因百科全书和基因组通路(KEGG)分析显示,SB431542 组的造血细胞谱系通路显著下调。SB431542防止NZB/W小鼠脾脏和肾实质中的B细胞浸润CD20+细胞)以及抗dsDNA抗体(IgG)的血清水平。此外,qRT-PCR和免疫组织化学证实SB431542抑制TLR9TGFβ1PDGFB的产生。

总之,该研究表明,SB431542NZB/W小鼠中抑制蛋白尿并改善组织学损伤。GOKEGG分析鉴定了与B细胞抑制高度相关的术语和通路。此外,SB431542治疗不仅可以抑制脾脏和肾脏中的B细胞浸润,还可以下调这些小鼠的全身和局部TLR9/TGFβ1/PDGFB 信号传导。然而,具有免疫调节活性的SB431542LN治疗中的重要价值需要进一步研究

 

出处:Xia Y, Jiang C, Yang M, Liu T, Zou X, Li C, Wang X. SB431542 alleviates lupus nephritis by regulating B cells and inhibiting the TLR9/TGFβ1/PDGFB signaling. J Autoimmun. 2022 Aug 26;132:102894. doi: 10.1016/j.jaut.2022.102894. Epub ahead of print. PMID: 36030617.

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    2023-04-03 lilianxiang
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    2023-01-13 yuanming7
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    2023-03-21 changhe713
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    2022-09-03 villahu

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