Stat3 as a potential therapeutic target for rheumatoid arthritis

Oike, Takatsugu; Sato, Yuiko; Kobayashi, Tami; Miyamoto, Kana; Nakamura, Satoshi; Kaneko, Yosuke; Kobayashi, Shū; Harato, Kengo; Saya, Hideyuki; Matsumoto, Morio; Nakamura, Masaya; Niki, Yasuo; Miyamoto, Takeshi

doi:10.1038/s41598-017-11233-w

Cited by 57 publications

(36 citation statements)

References 35 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, although a variety of biologic reagents for RA such as anti-TNF-α antibodies have been developed, molecular mechanisms involved in RA development remain largely unknown, and targeted therapy for RA patients has not been well established. 9,10 As a result, identifying new biomarkers for RA can provide new insight into understanding mechanisms underlying RA and helping with the diagnosis, treatment, and prognosis prediction of this disease. Accumulating studies have implicated that non-coding RNAs play an important role in RA, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs).…”

Section: Introductionmentioning

confidence: 99%

MiR‐548a‐3p regulates inflammatory response via TLR4/NF‐κB signaling pathway in rheumatoid arthritis

Wang

Zheng

Gao

et al. 2018

J of Cellular Biochemistry

View full text Add to dashboard Cite

Currently published studies have implicated that microRNAs (miRNAs) including exosomes-encapsulated miRNAs play a critical role in rheumatoid arthritis (RA). Previously, we have found that exosomes-encapsulated miR-548a-3p was significantly decreased in serum samples from RA patients by miRNAs microarray analysis. However, little is known of the role of miR-548a-3p in the development and progression of RA. In this study, we aim to investigate the underlying molecular mechanisms of miR-548a-3p in RA, which will provide new insight into understanding the pathogenesis of RA and identifying novel therapeutics targets for this disease. As validated by quantitative real-time polymerase chain reaction (qRT-PCR), the expression of miR-548a-3p in serum exosomes and peripheral blood mononuclear cells (PBMCs) of RA patients (n = 76) was obviously down-regulated compared with healthy controls (n = 20). Serum exosomal miR-548a-3p was negatively associated with levels of CRP, RF, and ESR in serum of patients with RA. MiR-548a-3p could inhibit the proliferation and activation of pTHP-1 cells by regulating the TLR4/NF-κB signaling pathway. Accordingly, exosomes-delivered miR-548a-3p may be a critical factor predicting the disease activity of RA. MiR-548a-3p/TLR4/NF-κB axis can serve as promising targets for RA diagnosis and treatment.

show abstract

Section: Introductionmentioning

confidence: 99%

MiR‐548a‐3p regulates inflammatory response via TLR4/NF‐κB signaling pathway in rheumatoid arthritis

Wang

Zheng

Gao

et al. 2018

J of Cellular Biochemistry

View full text Add to dashboard Cite

show abstract

“…via the phosphorylation of STAT3, and STAT3 stimulates joint inflammation and erosion in RA (35). Treatment with HJ significantly reduced the phosphorylation and expression of STAT3 in paw of cIA mice (Fig.…”

Section: Hj Suppresses the Expression Of Il-6 And Inhibits Stat3mentioning

confidence: 82%

Humulus japonicus extract ameliorates collagen‑induced arthritis in mice through regulation of overall articular inflammation

et al. 2019

View full text Add to dashboard Cite

Humulus japonicus (HJ) is a widely used herbal medicine in Asia with anti-oxidative, anti-microbial, and anti-inflammatory effects. We investigated the potential therapeutic effects of HJ in rheumatoid arthritis (RA) using a mouse model of collagen-induced arthritis (cIA) and a lipopolysaccharide-stimulated murine macrophage cell line (RAW 264.7). The cIA mice were administered 300 mg/kg HJ orally starting 3 days prior to second immunization. The clinical and histopathological findings were assessed in the paw of CIA mice. The levels of autoantibodies and inflammatory markers were determined in the plasma and cell culture supernatant, respectively. The expression at mRNA and protein levels was analyzed by reverse transcription quantitative-PcR and western blot analysis, respectively. HJ significantly decreased the gross arthritic scores and paw swelling in cIA mice. Furthermore, synovial inflammation, cartilage destruction, and bone erosion were markedly reduced by HJ. It also decreased the expression of inflammatory enzymes in both the paw of mice and RAW 264.7 cells. Moreover, the expression of genes related to all macrophages and pro-inflammatory M1 macrophage were significantly decreased, whereas the expression of anti-inflammatory M2 macrophage marker was markedly increased in the paw of HJ-treated cIA mice. In addition, HJ suppressed the levels of plasma anti-type II collagen antibody following the decreased expression of T helper type 1 (Th1) and Th2 cell-associated surface markers and cytokines in the paw. HJ also significantly inhibited the expression of IL-6 both in vitro and in vivo, followed by reduced STAT3 phosphorylation and expression in the paw of cIA mice. Finally, the expression of osteoclast-related genes was decreased in the paw of HJ-treated cIA mice. These findings suggest that HJ can play a role in suppressing the development of CIA by overall regulation of articular inflammation. This study should provide new insights into the use of HJ as a therapeutically effective natural product against RA.

show abstract

“…Especially, MMP‐2 and MMP‐9 are associated with the degradation of non‐collagen matrix components in the joints leading to exaggerated RA . Nuclear factor kappa B (NF‐κB) plays a central role in autoimmune diseases, it promotes inflammation and joint erosion in RA mouse models . Constitutive NF‐κB activation in synovial fluid cells is observed in patients with RA and NF‐κB inactivation blocked both joint destruction and inflammation in a CIA mouse model .…”

Section: Introductionmentioning

confidence: 99%

“…Nuclear factor kappa B (NF‐κB) plays a central role in autoimmune diseases, it promotes inflammation and joint erosion in RA mouse models . Constitutive NF‐κB activation in synovial fluid cells is observed in patients with RA and NF‐κB inactivation blocked both joint destruction and inflammation in a CIA mouse model . Thus, selective NF‐κB inhibitors might serve as potential agents for RA therapy.…”

Section: Introductionmentioning

confidence: 99%

Meroterpenoid‐Rich Fraction of the Ethanol Extract of Sargassum Serratifolium Suppresses Collagen‐Induced Rheumatoid Arthritis in DBA/1J Mice Via Inhibition of Nuclear Factor κB Activation

Joung

Kwon

Gwon

et al. 2020

Molecular Nutrition Food Res

View full text Add to dashboard Cite

Scope: Rheumatoid arthritis (RA) is an autoimmune disorder related to the inflammation of cartilage due to the infiltration of inflammatory cells. Sargassum serratifolium, a brown alga, possesses strong anti-inflammatory activities. Methods and Results: The effect of meroterpenoid-rich fraction from the ethanol extract of S. serratifolium (MES) on RA and its underlying mechanisms on the inhibition of RA using a collagen-induced arthritis (CIA) mouse model are examined. The results show that MES ameliorates paw swelling and reduces the arthritis score. MES considerably decreases the secretion of pro-inflammatory cytokines in the serum and joint tissue of mice. Histopathological analysis demonstrates that MES strongly inhibited bone damage and inflammatory cell intrusion in the joint tissue.

show abstract

Stat3 as a potential therapeutic target for rheumatoid arthritis

Cited by 57 publications

References 35 publications

MiR‐548a‐3p regulates inflammatory response via TLR4/NF‐κB signaling pathway in rheumatoid arthritis

MiR‐548a‐3p regulates inflammatory response via TLR4/NF‐κB signaling pathway in rheumatoid arthritis

Humulus japonicus extract ameliorates collagen‑induced arthritis in mice through regulation of overall articular inflammation

Meroterpenoid‐Rich Fraction of the Ethanol Extract of Sargassum Serratifolium Suppresses Collagen‐Induced Rheumatoid Arthritis in DBA/1J Mice Via Inhibition of Nuclear Factor κB Activation

Contact Info

Product

Resources

About