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HIF1 alpha inhibition facilitates Leflunomide-AHR-CRP signaling to attenuate bone erosion in CRP-aberrant rheumatoid arthritis 期刊论文

编号：

8f6a1387-4d00-47f0-acce-b41ea58ff8aa
作者：

Liang, Chao#^[1,2,3]Li, Jie#^[4]Lu, Cheng#^[1,2,3,5]Xie, Duoli^[1,2,3];Liu, Jin^[1,2,3];Zhong, Chuanxin^[1,2,3];Wu, Xiaohao^[1,2,3];Dai, Rongchen^[1,2,3];Zhang, Huarui^[1,2,3];Guan, Daogang^[1,2,3];Guo, Baosheng^[1,2,3];He, Bing^[1,2,3];Li, Fangfei^[1,2,3];He, Xiaojuan^[1,2,3,5];Zhang, Wandong^[6];Zhang, BaoTing^[4];Zhang, Ge*^[1,2,3]Lu, Aiping^[1,2,3,7]
语种：

英文
期刊：

NATURE COMMUNICATIONS ISSN：2041-1723 2019 年 10 卷 ; OCT 8
收录：
摘要：

Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by progressive bone erosion. Leflunomide is originally developed to suppress inflammation via its metabolite A77 1726 to attenuate bone erosion. However, distinctive responsiveness to Leflunomide is observed among RA individuals. Here we show that Leflunomide exerts immunosuppression but limited efficacy in RA individuals distinguished by higher serum C-reactive protein (CRPHigher, CRPH), whereas the others with satisfactory responsiveness to Leflunomide show lower CRP (CRPLower, CRPL). CRP inhibition decreases bone erosion in arthritic rats. Besides the immunomodulation via A77 1726, Leflunomide itself induces AHR-ARNT interaction to inhibit hepatic CRP production and attenuate bone erosion in CRPL arthritic rats. Nevertheless, high CRP in CRPH rats upregulates HIF1 alpha, which competes with AHR for ARNT association and interferes Leflunomide-AHR-CRP signaling. Hepatocyte-specific HIF1 alpha deletion or a HIF1 alpha inhibitor Acriflavine re-activates Leflunomide-AHR-CRP signaling to inhibit bone erosion. This study presents a precision medicine-based therapeutic strategy for RA.
推荐引用方式
GB/T 7714：

Liang Chao,Li Jie,Lu Cheng, et al. HIF1 alpha inhibition facilitates Leflunomide-AHR-CRP signaling to attenuate bone erosion in CRP-aberrant rheumatoid arthritis [J].NATURE COMMUNICATIONS,2019,10.
APA：

Liang Chao,Li Jie,Lu Cheng,Xie Duoli,&Lu Aiping.(2019).HIF1 alpha inhibition facilitates Leflunomide-AHR-CRP signaling to attenuate bone erosion in CRP-aberrant rheumatoid arthritis .NATURE COMMUNICATIONS,10.
MLA：

Liang Chao, et al. "HIF1 alpha inhibition facilitates Leflunomide-AHR-CRP signaling to attenuate bone erosion in CRP-aberrant rheumatoid arthritis" .NATURE COMMUNICATIONS 10(2019).
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