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Wutou decoction attenuates rheumatoid arthritis by modulating the Ahr/LOC101928120/SHC1 pathway
Pharmaceutical Biology ( IF 3.9 ) Pub Date : 2021-06-29 , DOI: 10.1080/13880209.2021.1941131
Dan Wu 1 , Xi Li 1 , Jun Liu 1 , Can Hu 1 , Jiefang Li 1
Affiliation  

Abstract

Context

Wutou decoction (WTD) is a Chinese herbal formula alleviating rheumatoid arthritis (RA). SHC adaptor protein 1 (SHC1) regulates apoptosis, inflammation, and the production of reactive oxygen species (ROS). The LOC101928120 gene is located near the SHC1 gene. Bioinformatics analysis showed that the long non-coding RNA LOC101928120 binds to histone deacetylase HDAC1 that might regulate SHC1 expression. The LOC101928120 gene might be targeted by the transcriptional factor Aryl hydrocarbon receptor (Ahr).

Objective

This study determines the involvement of the Ahr/LOC101928120/SHC1 pathway in WTD alleviation of RA.

Materials and methods

Wistar rats were injected with complete Freund’s adjuvant in the hind footpad to construe the RA model. WTD (9.8 g/kg/day) was administered intragastrically for 15 days. The CHON-001 chondrocyte cells were treated with IL-1β (10 ng/mL) alone or in combination with WTD (1 μg/mL). A RNA pull-down assay was performed to determine the interaction between LOC101928120 and HDAC1. Ahr targeting the LOC101928120 gene was detected using luciferase reporter and chromatin immunoprecipitation assays.

Results

WTD alleviated the swelling of the hind paw in rats with RA and suppressed the chondrocyte apoptosis and ROS production caused by IL-1β. WTD decreased SHC1 but increased LOC101928120 in IL-1β-treated chondrocytes. SHC1 knockdown and LOC101928120 overexpression also showed the protection. However, LOC101928120 knockdown attenuated the protective effects of WTD. WTD stimulated Ahr, which promoted LOC101928120 transcription. LOC101928120 recruited HDAC1 to the promoter region of the SHC1 gene, thereby decreasing SHC1.

Discussion and conclusion

This study revealed a new mechanism by which WTD alleviates RA by modulating the Ahr/LOC101928120/SHC1 pathway.



中文翻译:

五头汤通过调节Ahr/LOC101928120/SHC1通路减轻类风湿性关节炎

摘要

语境

五头汤(WTD)是一种缓解类风湿性关节炎(RA)的中草药配方。SHC 衔接蛋白 1 (SHC1) 调节细胞凋亡、炎症和活性氧 (ROS) 的产生。该LOC101928120基因位于靠近SHC1基因。生物信息学分析表明,长链非编码 RNA LOC101928120 与可能调节 SHC1 表达的组蛋白脱乙酰酶 HDAC1 结合。所述LOC101928120基因可能是由转录因子芳香烃受体(AHR)被靶向。

客观的

本研究确定了 Ahr/LOC101928120/SHC1 通路参与减轻 RA 的 WTD。

材料和方法

Wistar 大鼠后足垫注射完全弗氏佐剂以构建 RA 模型。WTD (9.8 g/kg/天) 灌胃给药 15 天。CHON-001 软骨细胞用单独的 IL-1β (10 ng/mL) 或与 WTD (1 μg/mL) 组合处理。进行 RNA 下拉测定以确定 LOC101928120 和 HDAC1 之间的相互作用。使用荧光素酶报告基因和染色质免疫沉淀测定法检测到靶向LOC101928120基因的Ahr 。

结果

WTD减轻了RA大鼠后爪肿胀,抑制了IL-1β引起的软骨细胞凋亡和ROS产生。WTD 减少了 SHC1,但增加了 IL-1β 处理的软骨细胞中的 LOC101928120。SHC1 敲低和 LOC101928120 过表达也显示出保护作用。然而,LOC101928120 敲低减弱了 WTD 的保护作用。WTD 刺激 Ahr,促进 LOC101928120 转录。LOC101928120 将 HDAC1 募集到SHC1基因的启动子区域,从而减少 SHC1。

讨论与结论

这项研究揭示了 WTD 通过调节 Ahr/LOC101928120/SHC1 通路减轻 RA 的新机制。

更新日期:2021-06-29
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