SIRT1 inhibits rheumatoid arthritis fibroblast-like synoviocyte aggressiveness and inflammatory response via suppressing NF-κB pathway

Li, Guoqing; Xia, Zhongbing; Liu, Ying; Meng, Fanru; Wu, Xia; Fang, Yu; Zhang, Chunwang; Liú, Dan

doi:10.1042/bsr20180541

Cited by 69 publications

(53 citation statements)

References 37 publications

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“…Treated RA-FLS. Recently, many studies showed that NF-κB signaling is crucial for the RA process, especially in the proinflammatory cytokine production in FLS [4,9,16]. Therefore, we detected the effect of USP5 on IL-1β-induced NF-κB activation.…”

Section: Usp5 Promoted Nf-κb Signaling Activation In Il-1β-mentioning

confidence: 85%

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Proinflammatory Effects of Ubiquitin-Specific Protease 5 (USP5) in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

Luo

Liu

et al. 2020

Mediators of Inflammation

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Rheumatoid arthritis (RA) is a worldwide chronic autoimmune inflammatory disease which is affecting approximately 1% of the total population. It is characterized by abnormal proliferation of fibroblast-like synoviocytes (FLS) and increased production of proinflammatory cytokines. In the current study, we were aiming to investigate the role of ubiquitin-specific protease 5 (USP5) in the inflammatory process in RA-FLS. Expression of USP5 was found upregulated in RA-FLS compared with that in osteoarthritis- (OA-) FLS, and IL-1β stimulation increased USP5 expression in a time-dependent manner. Furthermore, we found that USP5 overexpression significantly aggravated proinflammatory cytokine production and related nuclear factor κB (NF-κB) signaling activation. Consistently, silencing of USP5 decreased the release of cytokines and inhibited the activation of NF-κB. In addition, USP5 was found to interact with tumor necrosis factor receptor-associated factor 6 (TRAF6) and remove its K48-linked polyubiquitination chains therefore stabilizing TRAF6. Our data showed that a USP5-positive cell regulates inflammatory processes in RA-FLS and suggested USP5 as a potential target for RA treatment.

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Section: Usp5 Promoted Nf-κb Signaling Activation In Il-1β-mentioning

confidence: 85%

“…Fibroblast-like synoviocytes (FLS) are a special type of mesenchymal-derived cells lining the layer of normal synovial tissues [4]. In RA patients, FLS surprisingly express some phenotypes similar to tumor cells that are described as unregulated proliferation, resistance to apoptosis, and insensitivity to contact inhibition [5].…”

Section: Introductionmentioning

confidence: 99%

Proinflammatory Effects of Ubiquitin-Specific Protease 5 (USP5) in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

Luo

Liu

et al. 2020

Mediators of Inflammation

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show abstract

“…5a, b). SIRT1 is well known to reduce in ammation by regulation of NF-κB expression [45][46][47][48][49]. Accordingly, we investigated NF-κB expression in primary glial cells.…”

Section: Sirt1 Expression Is Decreased In Brains Of Ad Patients and Imentioning

confidence: 99%

Reducing miR485-3p ameliorates Alzheimer`s disease pathology by regulation of amyloid beta and neuro-inflammation

Koh¹,

Jang²,

Tae³

et al. 2020

Preprint

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Background Alzheimer`s disease (AD) is a progressive neurodegenerative disease worldwide. Accumulation of amyloid-β (Aβ), neurofibrillary tangles and neuroinflammation play the important neuro-pathology in patients with AD. miRNA is multifunctional and involved in physiological and pathological processes. Recently, microRNAs have been linked to neurodegenerative diseases. However, it is little known whether miRNA dysregulation contributes to AD pathology progression such as Ab processing, phagocytosis and neuroinflammation. Here, we identify miR485-3p as a novel modulator of AD pathology in 5XFAD mice. Methods To study the role of miR485-3p in AD, we used in control or miR485-3p antisense oligonucleotides (miR485-3p ASO) injected 5XFAD mouse model. Changes of Ab processing, clearance and inflammation were analyzed by biochemical method in vitro and in vivo. Results This study suggests that miR485-3p, a novel miRNA targeting SIRT1 may contribute to pathogenesis in an AD mouse. We found SIRT1 is significantly reduced in the precentral gyrus of Alzheimer patient`s and in 5XFAD mice. To determine whether the inhibition of miRNA 485-3p would affect AD pathology, we studied the effect of the antisense oligo in the brain of 5XFAD mice through direct intracerebral ventricular injection with miR485-3p ASO. We demonstrated that miR485-3p ASO significantly reduced Aβ plaque and amyloid biosynthetic enzyme. Importantly, the attenuation of Aβ plaques through miR485-3p ASO was mediated through Aβ phagocytic activity of glial cells, by which it can directly target CD36. MiR485-3p ASO also decreased inflammatory responses. Collectively, these responses inhibited neuronal loss caused by Aβ lead to improvements of cognitive impairment. Conclusion Our data provide evidence for the molecular mechanisms which underlie the miR485-3p ASO responses in an AD mouse model. These results suggest that attenuating miRNA 485-3p levels might represent a novel therapeutic approach in AD.

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“…5a, b). SIRT1 is well known to reduce inflammation by regulation of NF-B expression [45][46][47][48][49]. Accordingly, we investigated NF-B expression in primary glial cells.…”

Section: Previous Studies Have Shown That Glial Cells Mediate Clearanmentioning

confidence: 99%

Reducing miR485-3p ameliorates Alzheimer`s disease pathology by regulation of amyloid beta and neuro-inflammation

Koh¹,

Jang²,

Tae³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Alzheimer`s disease (AD) is a progressive neurodegenerative disease worldwide. Accumulation of amyloid-β (Aβ), neurofibrillary tangles and neuroinflammation play the important neuro-pathology in patients with AD. miRNA is multifunctional and involved in physiological and pathological processes. Recently, microRNAs have been linked to neurodegenerative diseases. However, it is little known whether miRNA dysregulation contributes to AD pathology progression such as Aβ processing, phagocytosis and neuroinflammation. Here, we identify miR485-3p as a novel modulator of AD pathology in 5XFAD mice. Methods To study the role of miR485-3p in AD, we used in control or miR485-3p antisense oligonucleotides (miR485-3p ASO) injected 5XFAD mouse model. Changes of Aβ processing and clearance and inflammation were analyzed by biochemical method in vitro and in vivo. Result This study suggests that miR485-3p, a novel miRNA targeting SIRT1 may contribute to pathogenesis in an AD mouse. We found SIRT1 is significantly reduced in the precentral gyrus of Alzheimer patient`s and in 5XFAD mice. To determine whether the inhibition of miRNA 485-3p would affect AD pathology, we studied the effect of the antisense oligo in the brain of 5XFAD mice through direct intracerebral ventricular injection with miR485-3p ASO. We demonstrated that miR485-3p ASO significantly reduced Aβ plaque and amyloid biosynthetic enzyme. Importantly, the attenuation of Aβ plaques through miR485-3p ASO was mediated through Aβ phagocytic activity of glial cells, by which it can directly target CD36. MiR485-3p ASO also decreased inflammatory responses. Collectively, these responses inhibited neuronal loss caused by Aβ lead to improvements of cognitive impairment. Conclusion Our data provide evidence for the molecular mechanisms which underlie the miR485-3p ASO responses in an AD mouse model. These results suggest that attenuating miRNA 485-3p levels might represent a novel therapeutic approach in AD.

show abstract

SIRT1 inhibits rheumatoid arthritis fibroblast-like synoviocyte aggressiveness and inflammatory response via suppressing NF-κB pathway

Cited by 69 publications

References 37 publications

Proinflammatory Effects of Ubiquitin-Specific Protease 5 (USP5) in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

Proinflammatory Effects of Ubiquitin-Specific Protease 5 (USP5) in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

Reducing miR485-3p ameliorates Alzheimer`s disease pathology by regulation of amyloid beta and neuro-inflammation

Reducing miR485-3p ameliorates Alzheimer`s disease pathology by regulation of amyloid beta and neuro-inflammation

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