scholarly journals Treatment effect of CDKN1A on rheumatoid arthritis by mediating proliferation and invasion of fibroblast-like synoviocytes cells

2018 ◽  
Vol 194 (2) ◽  
pp. 220-230 ◽  
Author(s):  
X. Gang ◽  
H. Xu ◽  
L. Si ◽  
X. Zhu ◽  
T. Yu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Treatment Effect ◽  
Proliferation And Invasion ◽  
Fibroblast Like Synoviocytes

scholarly journals The GTPase Rac Regulates the Proliferation and Invasion of Fibroblast-Like Synoviocytes from Rheumatoid Arthritis Patients

2007 ◽  
Vol 13 (5-6) ◽  
pp. 297-304 ◽  
Author(s):  
Amanda Chan ◽  
Mumtaz Akhtar ◽  
Max Brenner ◽  
Yi Zheng ◽  
Percio S Gulko ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Proliferation And Invasion ◽  
Fibroblast Like Synoviocytes ◽  
Gtpase Rac

scholarly journals Antioxidant Carbon Nanoparticles Inhibit Fibroblast-Like Synoviocyte Invasiveness and Reduce Disease Severity in a Rat Model of Rheumatoid Arthritis

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1005
Author(s):  
Mark R. Tanner ◽  
Redwan Huq ◽  
William K. A. Sikkema ◽  
Lizanne G. Nilewski ◽  
Nejla Yosef ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Severity ◽  
Hydroxyl Radicals ◽  
Rat Model ◽  
Poly Ethylene Glycol ◽  
Poly Ethylene ◽  
Reduce Disease Severity ◽  
Proliferation And Invasion ◽  
Fibroblast Like Synoviocytes

Reactive oxygen species have been involved in the pathogenesis of rheumatoid arthritis (RA). Our goal was to determine the effects of selectively scavenging superoxide (O2•−) and hydroxyl radicals with antioxidant nanoparticles, called poly(ethylene glycol)-functionalized hydrophilic carbon clusters (PEG-HCCs), on the pathogenic functions of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) and on the progression of an animal model of RA. We used human FLS from patients with RA to determine PEG-HCC internalization and effects on FLS cytotoxicity, invasiveness, proliferation, and production of proteases. We used the pristane-induced arthritis (PIA) rat model of RA to assess the benefits of PEG-HCCs on reducing disease severity. PEG-HCCs were internalized by RA-FLS, reduced their intracellular O2•−, and reduced multiple measures of their pathogenicity in vitro, including proliferation and invasion. In PIA, PEG-HCCs caused a 65% reduction in disease severity, as measured by a standardized scoring system of paw inflammation and caused a significant reduction in bone and tissue damage, and circulating rheumatoid factor. PEG-HCCs did not induce lymphopenia during PIA. Our study demonstrated a role for O2•− and hydroxyl radicals in the pathogenesis of a rat model of RA and showed efficacy of PEG-HCCs in treating a rat model of RA.

scholarly journals Linc02381 Exacerbates Rheumatoid Arthritis Through Adsorbing miR-590-5p and Activating the Mitogen-Activated Protein Kinase Signaling Pathway in Rheumatoid arthritis-fibroblast-like synoviocytes

2020 ◽  
Vol 29 ◽  
pp. 096368972093802
Author(s):  
Jing Wang ◽  
Qing Zhao
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Protein Kinase ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Synovial Tissues ◽  
Proliferation And Invasion ◽  
Fibroblast Like Synoviocytes

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. New evidence suggested that linc02381 suppressed colorectal cancer progression by regulating PI3 K signaling pathway, but the role of linc02381 in other diseases, such as RA, remains unclear. This study aimed to reveal the mechanism of linc02381 in RA progression. In vivo and in vitro, we found that linc02381 was upregulated in RA synovial tissues or RA fibroblast-like synoviocytes (RA-FLSs, P < 0.01), which were detected by quantitative real-time polymerase chain reaction. Cell Counting Kit-8, EDU, and Transwell assays revealed that linc02381 overexpression enhanced cell proliferation and invasion, and linc02381 knockdown inhibited cell proliferation and invasion in FLSs. Moreover, the results of bioinformatics analysis, luciferase reporter gene assay, and pull-down assay verified that linc02381 could directly bind with miR-590-5p. MiR-590-5p was downregulated in RA-FLSs, and overexpression of linc02381 suppressed expression of miR-590-5p that post-transcriptionally suppressed the expression of mitogen-activated protein kinase kinase 3 (MAP2K3), and overexpression of miR-590-5p reversed the effect of linc02381 overexpression on MAP2K3 expression. MiR-590-5p inhibitor reversed the inhibition effect of linc02381 knockdown on proliferation and invasion of FLSs, which enhanced expression of MAP2K3, and activation of p38 and AP-1 in the MAPK signaling pathway. In summary, linc02381 was upregulated in RA synovial tissues and RA-FLSs, and it exacerbated RA by adsorbing miR-590-5p to activate the MAPK signaling pathway.

scholarly journals Knockdown of nrf2 exacerbates TNF-α-induced proliferation and invasion of rheumatoid arthritis fibroblast-like synoviocytes through activating JNK pathway

2020 ◽  
Author(s):  
Yu Du ◽  
Qian Wang ◽  
Na Tian ◽  
Meng Lu ◽  
Xian-Long Zhang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Western Blot ◽  
Nuclear Translocation ◽  
Cell Counting ◽  
Related Factor ◽  
Jnk Pathway ◽  
Tnf Α ◽  
Synovial Tissues ◽  
Proliferation And Invasion ◽  
Fibroblast Like Synoviocytes

Abstract Background. Fibroblast-like synoviocytes (FLS) in the synovial tissue of rheumatoid arthritis (RA) exhibit over-proliferative and aggressive phenotypes, which participate in the pathophysiology of RA. In RA, little is known about the non-antioxidant effect of nuclear factor erythroid 2-related factor 2 (nrf2), master regulator of redox homeostasis. In this study, we explored the expression and upstream regulatory factors of nrf2, and revealed its functions in modulating the proliferation and invasion in RA-FLS. Methods. FLS were isolated from RA and osteoarthritis patients. Expression of nrf2 in the synovial tissues and FLS was analyzed by immunohistochemistry, real-time PCR, western blot, and immunofluorescence. Cell proliferation was examined by Cell Counting Kit-8, and cell invasion was tested by transwell assay. Phosphorylation of JNK was determined by Western blot. Results. Nrf2 expression in the RA synovial tissues was upregulated. TNF-α promoted expression and nuclear translocation of nrf2 in RA-FLS, and increased the intracellular reactive oxygen species (ROS) level. Nrf2 nuclear translocation was blocked by ROS inhibitor N-acetylcysteine. Both knockdown of nrf2 by siRNA and inhibition of nrf2 by ML385 significantly promoted the TNF-α-induced proliferation and invasion of RA-FLS. Activation of nrf2 by sulforaphane (SFN) profoundly inhibited the TNF-α-induced proliferation and invasion of RA-FLS. Knockdown of nrf2 also enhanced the TNF-α-induced matrix metalloproteinases (MMPs) expression and phosphorylation of JNK in RA-FLS. Proliferation and invasion of RA-FLS incubated with TNF-α and nrf2 siRNA was inhibited by pre-treatment with JNK inhibitor SP600125. Conclusion. Taken together, nrf2 is over-expressed in synovial tissues of RA patients, which may be induced by TNF-α and ROS levels. Increased nrf2 may suppress TNF-α-induced proliferation, invasion, and MMPs expression in RA-FLS through inhibiting JNK activation, indicating that nrf2 plays a protective role to relieve the severity of synovitis in RA.

scholarly journals Knockdown of nrf2 Exacerbates TNF-α-Induced Proliferation and Invasion of Rheumatoid Arthritis Fibroblast-Like Synoviocytes through Activating JNK Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Yu Du ◽  
Qian Wang ◽  
Na Tian ◽  
Meng Lu ◽  
Xian-Long Zhang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Western Blotting ◽  
Nuclear Translocation ◽  
Cell Counting ◽  
Related Factor ◽  
Jnk Pathway ◽  
Tnf Α ◽  
Synovial Tissues ◽  
Proliferation And Invasion ◽  
Fibroblast Like Synoviocytes

Fibroblast-like synoviocytes (FLS) in the synovial tissue of rheumatoid arthritis (RA) exhibit over-proliferative and aggressive phenotypes, which participate in the pathophysiology of RA. In RA, little is known about the nonantioxidant effect of nuclear factor erythroid 2-related factor 2 (nrf2), the master regulator of redox homeostasis. In this study, we aimed to explore the expression and upstream regulatory factors of nrf2 and revealed its functions in modulating the proliferation and invasion in RA-FLS. FLS were isolated from RA and osteoarthritis patients. Expression of nrf2 in the synovial tissues and FLS was analyzed by immunohistochemistry, real-time PCR, Western blotting, and immunofluorescence staining. Cell proliferation was examined by Cell Counting Kit-8. Cell invasion was tested by transwell assay. Phosphorylation of JNK was determined by Western blotting. The results showed that nrf2 expression in the RA synovial tissues was upregulated. TNF-α promoted expression and nuclear translocation of nrf2 in RA-FLS and increased the intracellular reactive oxygen species (ROS) level. Nrf2 nuclear translocation was blocked by ROS inhibitor N-acetylcysteine. Both knockdown of nrf2 by siRNA and inhibition of nrf2 by ML385 significantly promoted the TNF-α-induced proliferation and invasion of RA-FLS. Activation of nrf2 by sulforaphane (SFN) profoundly inhibited the TNF-α-induced proliferation and invasion of RA-FLS. Knockdown of nrf2 also enhanced the TNF-α-induced matrix metalloproteinases (MMPs) expression and phosphorylation of JNK in RA-FLS. Proliferation and invasion of RA-FLS incubated with TNF-α and nrf2 siRNA were inhibited by pretreatment with JNK inhibitor SP600125. In conclusion, nrf2 is overexpressed in synovial tissues of RA patients, which may be promoted by TNF-α and ROS levels. Activation of nrf2 may suppress TNF-α-induced proliferation, invasion, and MMPs expression in RA-FLS by inhibiting JNK activation, indicating that nrf2 plays a protective role in relieving the severity of synovitis in RA. Our results might provide novel insights into the treatment of RA.

The Role of miR-382-5p in Rheumatoid Arthritis: An In Vitro Study with Fibroblast-Like Synoviocytes

2020 ◽  
Vol 10 (2) ◽  
pp. 169-175
Author(s):  
Deqian Meng ◽  
Wenyou Pan ◽  
Ju Li
Keyword(s):  
Rheumatoid Arthritis ◽  
In Vitro Study ◽  
Underlying Mechanism ◽  
High Morbidity ◽  
Systemic Autoimmunity ◽  
Autoimmune Inflammatory Disease ◽  
Proliferation And Invasion ◽  
Fibroblast Like Synoviocytes

Rheumatoid arthritis (RA) is a common autoimmune inflammatory disease with high morbidity. MiR-382-5p may be associated with progression from systemic autoimmunity to RA inflammation. The present study aims to investigate the underlying mechanism of miR-382-5p in the pathogenesis of RA. In present study, the decreased expression of miR-382-5p was observed in RA-FLSs. Furthermore, miR-382-5p overexpression inhibited the proliferation and invasion of RA-FLS cells. In addition, miR-382-5p overexpression inhibited the release of inflammatory cytokines and promoted apoptosis of RA-FLS cells. Finally, miR-382-5p overexpression induced inactivation of TLR4/NF-κB/Cox2 signaling pathway. Our findings implied that miR-382-5p exerts regulative effect on pathogenesis of RA and indicated that miR-382-5p may represent as an effective therapeutic target in the clinical treatment of RA.

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