Metabolites as drivers and targets in rheumatoid arthritis.
Metabolites as drivers and targets in rheumatoid arthritis.
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代谢物作为类风湿性关节炎的驱动力和靶点。
DOI：
10.1093/cei/uxab021
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发表时间：
2022-06-11
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
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作者：
类风湿性关节炎（RA）是一种以新生血管形成、免疫细胞浸润和滑膜增生为特征的慢性自身免疫性疾病，可导致关节软骨和骨的降解，进而导致功能障碍。血管生成失调、滑液缺氧和免疫细胞浸润导致炎症关节出现“生物能量危机”，进一步加剧滑液侵袭。一些研究已经研究了代谢，免疫和炎症之间的这种恶性循环以及代谢物在这些相互作用中的作用。为了增加这种复杂性，发炎的滑膜是多细胞组织，具有许多具有不同代谢要求的细胞亚群。代谢产物可以在疾病期间塑造免疫细胞亚群的炎性表型，并充当中央信号枢纽。在RA关节中，基质细胞和免疫细胞的能量需求增加导致代谢物如乳酸盐、柠檬酸盐和琥珀酸盐以及脂肪细胞因子的积累，这些代谢物可以调节下游信号传导途径。转录因子如HIF 1 α和mTOR可以作为代谢传感器来激活滑膜细胞并驱动促炎效应子功能，从而使慢性炎症进一步持续。这些代谢中间体可能是潜在的治疗靶点，因此了解RA中代谢物和滑膜细胞之间的复杂相互作用可能有助于识别新的治疗策略，但也可能为疾病发病机制的潜在机制提供重要见解。RA炎症关节的不利微环境迫使细胞改变其代谢途径，以维持其致病激活状态。代谢产物作为影响多种细胞功能和进一步驱动炎症的信号通路的中心枢纽。
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by neovascularization, immune cell infiltration, and synovial hyperplasia, which leads to degradation of articular cartilage and bone, and subsequent functional disability. Dysregulated angiogenesis, synovial hypoxia, and immune cell infiltration result in a ‘bioenergetic crisis’ in the inflamed joint which further exacerbates synovial invasiveness. Several studies have examined this vicious cycle between metabolism, immunity, and inflammation and the role metabolites play in these interactions. To add to this complexity, the inflamed synovium is a multicellular tissue with many cellular subsets having different metabolic requirements. Metabolites can shape the inflammatory phenotype of immune cell subsets during disease and act as central signalling hubs. In the RA joint, the increased energy demand of stromal and immune cells leads to the accumulation of metabolites such as lactate, citrate, and succinate as well as adipocytokines which can regulate downstream signalling pathways. Transcription factors such as HIF1ɑ and mTOR can act as metabolic sensors to activate synovial cells and drive pro-inflammatory effector function, thus perpetuating chronic inflammation further. These metabolic intermediates may be potential therapeutic targets and so understanding the complex interplay between metabolites and synovial cells in RA may allow for identification of novel therapeutic strategies but also may provide significant insight into the underlying mechanisms of disease pathogenesis. The adverse microenvironment of the RA inflamed joint forces cells to switch their metabolic pathways in order to sustain their pathogenic activated status. Metabolites act as central hubs influencing multiple cellular functions and signaling pathways that further drive inflammation.
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影响因子：
16.6
作者：
Cruys B;Wong BW;Kuchnio A;Verdegem D;Cantelmo AR;Conradi LC;Vandekeere S;Bouché A;Cornelissen I;Vinckier S;Merks RM;Dejana E;Gerhardt H;Dewerchin M;Bentley K;Carmeliet P
通讯作者：
Carmeliet P
影响因子：
--
作者：
Evans, Laura;Williams, Anwen S.;Nowell, Mari
通讯作者：
Nowell, Mari
影响因子：
64.8
作者：
Bambouskova M;Gorvel L;Lampropoulou V;Sergushichev A;Loginicheva E;Johnson K;Korenfeld D;Mathyer ME;Kim H;Huang LH;Duncan D;Bregman H;Keskin A;Santeford A;Apte RS;Sehgal R;Johnson B;Amarasinghe GK;Soares MP;Satoh T;Akira S;Hai T;de Guzman Strong C;Auclair K;Roddy TP;Biller SA;Jovanovic M;Klechevsky E;Stewart KM;Randolph GJ;Artyomov MN
通讯作者：
Artyomov MN
影响因子：
29
作者：
Angelin A;Gil-de-Gómez L;Dahiya S;Jiao J;Guo L;Levine MH;Wang Z;Quinn WJ 3rd;Kopinski PK;Wang L;Akimova T;Liu Y;Bhatti TR;Han R;Laskin BL;Baur JA;Blair IA;Wallace DC;Hancock WW;Beier UH
通讯作者：
Beier UH
影响因子：
4.8
作者：
Dai, Qiaoding;Zhou, Di;Song, Xinwei
通讯作者：
Song, Xinwei