Rheumatoid arthritis and mitochondrial homeostasis: The crossroads of metabolism and immunity

Liu, Cui; Jing, Weiyao; Chenghong, Su; Limei, Liu; Xinghua, Zhang; Yuan, Bo; Xiaozheng, Du; Wang, Haidong

doi:10.3389/fmed.2022.1017650

Cited by 21 publications

(11 citation statements)

References 153 publications

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“…78 This process primarily encompasses mitochondrial biogenesis, altered dynamics, and autophagy. 79 Impaired mitochondrial biogenesis, resulting from the loss of mitochondrial DNA, has been implicated in RA development. Reduced mitochondrial autophagy prevents timely clearance of dysfunctional mitochondria, thereby exacerbating the onset of RA.…”

Section: Mitochondrial Homeostasismentioning

confidence: 99%

Matrine, a potential drug for the treatment of rheumatoid arthritis

Peng,

Lian,

Wang

et al. 2024

Rheumatology & Autoimmunity

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Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease with a multifaceted pathogenesis involving genetic, epigenetic, and environmental factors. It mainly targets the synovium, leading to synovitis and subsequently bone erosion. Novel effective treatments for RA are imperative. Matrine, the main active constituent of Sophora flavescens Ait (known as Kushen in Chinese medicine), has been used to treat fever, dysentery, hematochezia, jaundice, oliguria, vulvar swelling, asthma, eczema, and inflammatory disorders. Matrine exhibits diverse pharmacological effects, including antitumor, anti‐inflammatory, antifibrotic, and antiviral properties. Animal studies have suggested that matrine mitigates inflammation and reduces RA severity by modulating inflammation‐related expression. Its therapeutic mechanism in RA may involve several signaling pathways, including the phosphatidylinositol 3‐kinase/protein kinase B/mammalian target of the rapamycin, nuclear factor‐κB, Janus kinase/signal transducers and activators of transcription, and mitogen‐activated protein kinase pathways, all of which are associated with various biological processes, such as cell proliferation and differentiation, apoptosis, and immune regulation. Moreover, mitochondrial homeostasis disruption and epigenetic modifications, mediated by long noncoding RNAs, play crucial roles in RA pathogenesis. Experimental evidence suggests that matrine exerts therapeutic effects by modulating mitochondrial homeostasis and long noncoding RNAs. We summarize the molecular mechanisms of matrine in RA treatment to provide theoretical support for expanding its clinical applications to the treatment of RA.

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Section: Mitochondrial Homeostasismentioning

confidence: 99%

Matrine, a potential drug for the treatment of rheumatoid arthritis

Peng,

Lian,

Wang

et al. 2024

Rheumatology & Autoimmunity

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“…These factors can activate FLSs and mediate proliferation, anti-apoptosis, erosion, migration, and other pathological behaviors ( 53 , 54 ). Mitochondrial damage and oxidative stress can affect immune cell metabolic processes and promote inflammatory behavior ( 55 , 56 ). Additionally, ROS and the products of mitochondrial damage are good activators of inflammatory response.…”

Section: Role Of Ros and Mitochondrial Damage In Ra Inflammationmentioning

confidence: 99%

Role of reactive oxygen species and mitochondrial damage in rheumatoid arthritis and targeted drugs

et al. 2023

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Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation, pannus formation, and bone and cartilage damage. It has a high disability rate. The hypoxic microenvironment of RA joints can cause reactive oxygen species (ROS) accumulation and mitochondrial damage, which not only affect the metabolic processes of immune cells and pathological changes in fibroblastic synovial cells but also upregulate the expression of several inflammatory pathways, ultimately promoting inflammation. Additionally, ROS and mitochondrial damage are involved in angiogenesis and bone destruction, thereby accelerating RA progression. In this review, we highlighted the effects of ROS accumulation and mitochondrial damage on inflammatory response, angiogenesis, bone and cartilage damage in RA. Additionally, we summarized therapies that target ROS or mitochondria to relieve RA symptoms and discuss the gaps in research and existing controversies, hoping to provide new ideas for research in this area and insights for targeted drug development in RA.

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“…The mitochondrion is a semi-autonomous organelle with a double membrane structure, which can provide cell energy through the tricarboxylic acid cycle (TCA) oxidative phosphorylation ( 11 , 12 ). Previous studies have found that imbalances in mitochondrial homeostasis may contribute to the development of various autoimmune diseases including RA, scleroderma, desiccation syndrome and systemic lupus erythematosus ( 13 , 14 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of copper death-associated molecular clusters and immunological profiles in rheumatoid arthritis

Zhou

et al. 2023

Front. Immunol.

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ObjectiveAn analysis of the relationship between rheumatoid arthritis (RA) and copper death-related genes (CRG) was explored based on the GEO dataset.MethodsBased on the differential gene expression profiles in the GSE93272 dataset, their relationship to CRG and immune signature were analysed. Using 232 RA samples, molecular clusters with CRG were delineated and analysed for expression and immune infiltration. Genes specific to the CRGcluster were identified by the WGCNA algorithm. Four machine learning models were then built and validated after selecting the optimal model to obtain the significant predicted genes, and validated by constructing RA rat models.ResultsThe location of the 13 CRGs on the chromosome was determined and, except for GCSH. LIPT1, FDX1, DLD, DBT, LIAS and ATP7A were expressed at significantly higher levels in RA samples than in non-RA, and DLST was significantly lower. RA samples were significantly expressed in immune cells such as B cells memory and differentially expressed genes such as LIPT1 were also strongly associated with the presence of immune infiltration. Two copper death-related molecular clusters were identified in RA samples. A higher level of immune infiltration and expression of CRGcluster C2 was found in the RA population. There were 314 crossover genes between the 2 molecular clusters, which were further divided into two molecular clusters. A significant difference in immune infiltration and expression levels was found between the two. Based on the five genes obtained from the RF model (AUC = 0.843), the Nomogram model, calibration curve and DCA also demonstrated their accuracy in predicting RA subtypes. The expression levels of the five genes were significantly higher in RA samples than in non-RA, and the ROC curves demonstrated their better predictive effect. Identification of predictive genes by RA animal model experiments was also confirmed.ConclusionThis study provides some insight into the correlation between rheumatoid arthritis and copper mortality, as well as a predictive model that is expected to support the development of targeted treatment options in the future.

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Rheumatoid arthritis and mitochondrial homeostasis: The crossroads of metabolism and immunity

Cited by 21 publications

References 153 publications

Matrine, a potential drug for the treatment of rheumatoid arthritis

Matrine, a potential drug for the treatment of rheumatoid arthritis

Role of reactive oxygen species and mitochondrial damage in rheumatoid arthritis and targeted drugs

Identification of copper death-associated molecular clusters and immunological profiles in rheumatoid arthritis

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