Xie Bo, Lu Haojie, Xu Jinhui, Luo Haixin, Hu Yebei, Chen Yi, Geng Qingwei, Song Xiuzu
Zhejiang Chinese medical university, The Third People's hospital of Hangzhou, West Lake road 38, 310009 Hangzhou, People's Republic of China.
Zhejiang Chinese medical university, The Third People's hospital of Hangzhou, West Lake road 38, 310009 Hangzhou, People's Republic of China.
Joint Bone Spine. 2021 Mar;88(2):105099. doi: 10.1016/j.jbspin.2020.105099. Epub 2020 Nov 4.
This study was performed to investigate the multi-targets mechanism of hydroxychloroquine (HCQ) in the treatment of rheumatoid arthritis (RA).
The predicted targets of HCQ and the proteins related to RA were returned from databases. Followed by protein-protein interaction (PPI) network, the intersection of the two group of proteins was studied. Furthermore, gene ontology (GO) and KyotoEncyclopediaofGenesandGenomes (KEGG) enrichment was used to analyse these proteins in a macro perspective. Finally, the candidate targets were checked by molecular docking.
The results suggested that HCQ in the treatment of RA was mainly associated with 4 targets that are smoothened homolog (SMO), sphingosine kinase (SPHK) 1, SPHK2 and gatty-acid amide hydrolase (FAAH), with their related 3276 proteins' network which regulate ErbB, HIF-1, NF-κB, FoxO, chemokines, MAPK, PI3K/Akt pathways and so forth. Biological process were mainly focused in the regulation of cell activation, myeloid leukocyte activation, regulated exocytosis and so forth. Molecular docking analysis showed that hydrogen bonding and π-π stacking were the main forms of chemical force.
Our research provides protein targets affected by HCQ in the treatment of RA. SMO, SPHK1, SPHK2 and FAAH involving 3276 proteins become the multi-targets mechanism of HCQ in the treatment of RA.
本研究旨在探讨羟氯喹（HCQ）治疗类风湿关节炎（RA）的多靶点机制。
从数据库中检索HCQ的预测靶点和与RA相关的蛋白质。接着构建蛋白质-蛋白质相互作用（PPI）网络，研究两组蛋白质的交集。此外，利用基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析从宏观角度分析这些蛋白质。最后，通过分子对接验证候选靶点。
结果表明，HCQ治疗RA主要与4个靶点相关，即平滑同系物（SMO）、鞘氨醇激酶（SPHK）1、SPHK2和脂肪酸酰胺水解酶（FAAH），以及与它们相关的3276个蛋白质组成的网络，这些网络调节表皮生长因子受体（ErbB）、缺氧诱导因子-1（HIF-1）、核因子κB（NF-κB）、叉头转录因子O（FoxO）、趋化因子、丝裂原活化蛋白激酶（MAPK）、磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/Akt）等信号通路。生物学过程主要集中在细胞活化调节、髓样白细胞活化、调节性胞吐作用等方面。分子对接分析表明，氢键和π-π堆积是主要的化学作用力形式。
我们的研究提供了HCQ治疗RA时受影响的蛋白质靶点。涉及3276个蛋白质的SMO、SPHK1、SPHK2和FAAH成为HCQ治疗RA的多靶点机制。
