A20: a master regulator of arthritis

Wu, Yongyao; He, Xiaomin; Huang, Ning; Yu, Jiayun; Shao, Bin

doi:10.1186/s13075-020-02281-1

Cited by 25 publications

(28 citation statements)

References 112 publications

(208 reference statements)

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“…The ubiquitin-editing enzyme A20 (aka TNFAIP3) counteracts inflammatory signals and is important in the prevention of arthritis, as reviewed by Wu et al. ( 167 ). One mechanism by which A20 inhibits inflammation is through negative regulation of NLRP3 and caspase-1 activation, suppressing interleukin production and pyroptosis ( 167 , 168 ).…”

Section: The Nlrp3 Inflammasomementioning

confidence: 99%

“…( 167 ). One mechanism by which A20 inhibits inflammation is through negative regulation of NLRP3 and caspase-1 activation, suppressing interleukin production and pyroptosis ( 167 , 168 ). Myeloid-specific deletion of A20 results in a spontaneous polyarthritis with characteristics of RA, and deletion of NLRP3 could protect these mice from disease ( 168 ).…”

Section: The Nlrp3 Inflammasomementioning

confidence: 99%

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Mitochondria as Key Players in the Pathogenesis and Treatment of Rheumatoid Arthritis

et al. 2021

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Mitochondria are major energy-producing organelles that have central roles in cellular metabolism. They also act as important signalling hubs, and their dynamic regulation in response to stress signals helps to dictate the stress response of the cell. Rheumatoid arthritis is an inflammatory and autoimmune disease with high prevalence and complex aetiology. Mitochondrial activity affects differentiation, activation and survival of immune and non-immune cells that contribute to the pathogenesis of this disease. This review outlines what is known about the role of mitochondria in rheumatoid arthritis pathogenesis, and how current and future therapeutic strategies can function through modulation of mitochondrial activity. We also highlight areas of this topic that warrant further study. As producers of energy and of metabolites such as succinate and citrate, mitochondria help to shape the inflammatory phenotype of leukocytes during disease. Mitochondrial components can directly stimulate immune receptors by acting as damage-associated molecular patterns, which could represent an initiating factor for the development of sterile inflammation. Mitochondria are also an important source of intracellular reactive oxygen species, and facilitate the activation of the NLRP3 inflammasome, which produces cytokines linked to disease symptoms in rheumatoid arthritis. The fact that mitochondria contain their own genetic material renders them susceptible to mutation, which can propagate their dysfunction and immunostimulatory potential. Several drugs currently used for the treatment of rheumatoid arthritis regulate mitochondrial function either directly or indirectly. These actions contribute to their immunomodulatory functions, but can also lead to adverse effects. Metabolic and mitochondrial pathways are attractive targets for future anti-rheumatic drugs, however many questions still remain about the precise role of mitochondrial activity in different cell types in rheumatoid arthritis.

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Section: The Nlrp3 Inflammasomementioning

confidence: 99%

Section: The Nlrp3 Inflammasomementioning

confidence: 99%

Mitochondria as Key Players in the Pathogenesis and Treatment of Rheumatoid Arthritis

et al. 2021

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“…ZnF4 and ZnF7 bind to K63-or M1-linked polyubiquitin chains and exhibit E3 ligase activity. A20, which is reported to be an anti-inflammatory regulator, is involved in multiple regulatory mechanisms in cell death and inflammatory diseases [215]. The precise role of A20 in TNFα-induced cell death depends on the detailed physiological context.…”

Section: Cyldmentioning

confidence: 99%

Deubiquitinases: Modulators of Different Types of Regulated Cell Death

Lee

Kim

Hwang

et al. 2021

IJMS

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The mechanisms and physiological implications of regulated cell death (RCD) have been extensively studied. Among the regulatory mechanisms of RCD, ubiquitination and deubiquitination enable post-translational regulation of signaling by modulating substrate degradation and signal transduction. Deubiquitinases (DUBs) are involved in diverse molecular pathways of RCD. Some DUBs modulate multiple modalities of RCD by regulating various substrates and are powerful regulators of cell fate. However, the therapeutic targeting of DUB is limited, as the physiological consequences of modulating DUBs cannot be predicted. In this review, the mechanisms of DUBs that regulate multiple types of RCD are summarized. This comprehensive summary aims to improve our understanding of the complex DUB/RCD regulatory axis comprising various molecular mechanisms for diverse physiological processes. Additionally, this review will enable the understanding of the advantages of therapeutic targeting of DUBs and developing strategies to overcome the side effects associated with the therapeutic applications of DUB modulators.

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“…Более значимая ассоциация с псориатическим артритом, чем с псориазом, найдена для однонуклеотидного полиморфизма гена TNFAIP3 rs9321623 (C/T) [31]. Ген TNFAIP3 кодирует белок А20, также известный как TNF-α-индуцируемый белок 3 (TNFAIP3) [39]. Белок А20 связывается с белками сигнального пути NF-κB, в результате снижается активность транскрипционного фактора NF-κB и подавляется внутриклеточное прохождение сигнала, индуцированного цитокинами TNF-α, IL-1, IL-17 [40][41][42][43].…”

Section: разделunclassified

“…Мутации гена TNFAIP3 могут ослабить негативную регуляцию сигнального пути NF-κB белком А20, что приведет к повышению продукции провоспалительных цитокинов, включая TNF-α, IL -1β, IL-6, IL-18 [45]. Подтверждением данной гипотезы служат эксперименты, в которых показано, что у мышей с дефицитом белка А20 постоянно сохраняется активированным NF-κB, увеличивается уровень воспалительных цитокинов в сыворотке крови, повышается продукция TNF-α макрофагами, активируются процессы остеокластогенеза и развивается эрозивный полиартрит [39,46] Обнаружена ассоциация с развитием псориатического артрита у полиморфизма гена PTPN22 rs2476601 (1858C>T). Ген PTPN22 кодирует протеин-тирозинфосфатазу, нерецепторный тип 22 (лимфоидный) (PTPN22), которую называют также тирозинфосфатазой лимфоцитов.…”

Section: разделunclassified

Genetic markers for psoriatic arthritis in patients with psoriasis. Part I: non-HLA genes

Kubanov

Карамова

Чикин

et al. 2021

Vestnik dermatologii i venerologii

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Psoriatic arthritis often develops in patients with psoriasis and can lead to joint deformity, stiffness, dysfunction, and disability. Psoriatic arthritis is a polygenic disease. and the issue of personalizing the prognosis of its development can only be resolved taking into account the variability of plenty genomic loci associated with the development of the disease. The personification of the prognosis of the disease can be solved taking into account the variability of the set of genomic loci with which its development is associated. The review examines genomic polymorphisms associated with the development of psoriatic arthritis not psoriasis, except of HLA polymorphisms. Genome regions containing polymorphisms, allelic variants of which are associated both with the development of psoriatic arthritis and reducing the likelihood of its occurrence, are described. It has been reported that the predisposition to the development of psoriatic arthritis in patients with psoriasis is determined by genes encoding proteins involved in inflammation and bone metabolism.

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A20: a master regulator of arthritis

Cited by 25 publications

References 112 publications

Mitochondria as Key Players in the Pathogenesis and Treatment of Rheumatoid Arthritis

Mitochondria as Key Players in the Pathogenesis and Treatment of Rheumatoid Arthritis

Deubiquitinases: Modulators of Different Types of Regulated Cell Death

Genetic markers for psoriatic arthritis in patients with psoriasis. Part I: non-HLA genes

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