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Succinate/NLRP3 Inflammasome Induces Synovial Fibroblast Activation: Therapeutical Effects of Clematichinenoside AR on Arthritis

Overview of attention for article published in Frontiers in immunology, December 2016
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Title
Succinate/NLRP3 Inflammasome Induces Synovial Fibroblast Activation: Therapeutical Effects of Clematichinenoside AR on Arthritis
Published in
Frontiers in immunology, December 2016
DOI 10.3389/fimmu.2016.00532
Pubmed ID
Authors

Yi Li, Jia-Yi Zheng, Jian-Qun Liu, Jie Yang, Yang Liu, Chen Wang, Xiao-Nan Ma, Bao-Lin Liu, Gui-Zhong Xin, Li-Fang Liu

Abstract

Clematichinenoside AR (C-AR) is a triterpene saponin isolated from the root of Clematis manshurica Rupr., which is a herbal medicine used in traditional Chinese medicine for the treatment of arthritis. C-AR exerts anti-inflammatory and immunosuppressive properties, but little is known about its action in the suppression of fibroblast activation. Low oxygen tension and transforming growth factor-β (TGF-β1) induction in the synovium contribute to fibrosis in arthritis. This study was designed to investigate the effect of C-AR on synovial fibrosis from the aspects of hypoxic TGF-β1 and hypoxia-inducible transcription factor-1α (HIF-1α) induction. In the synovium of rheumatoid arthritis (RA) rats, hypoxic TGF-β1 induction increased succinate accumulation due to the reversal of succinate dehydrogenase (SDH) activation and induced NLRP3 inflammasome activation in a manner dependent on HIF-1α induction. In response to NLRP3 inflammasome activation, the released IL-1β further increased TGF-β1 induction, suggesting the forward cycle between inflammation and fibrosis in myofibroblast activation. In the synovium of RA rats, C-AR inhibited hypoxic TGF-β1 induction and suppressed succinate-associated NLRP3 inflammasome activation by inhibiting SDH activity, and thereby prevented myofibroblast activation by blocking the cross-talk between inflammation and fibrosis. Taken together, these results showed that succinate worked as a metabolic signaling, linking inflammation with fibrosis through NLRP3 inflammasome activation. These findings suggested that synovial succinate accumulation and HIF-1α induction might be therapeutical targets for the prevention of fibrosis in arthritis.

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The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 45 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 45 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 18%
Student > Bachelor 8 18%
Researcher 4 9%
Student > Postgraduate 3 7%
Student > Doctoral Student 2 4%
Other 6 13%
Unknown 14 31%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 15 33%
Pharmacology, Toxicology and Pharmaceutical Science 5 11%
Immunology and Microbiology 4 9%
Agricultural and Biological Sciences 3 7%
Medicine and Dentistry 1 2%
Other 2 4%
Unknown 15 33%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 December 2016.
All research outputs
#16,311,176
of 25,756,911 outputs
Outputs from Frontiers in immunology
#17,045
of 32,318 outputs
Outputs of similar age
#242,969
of 422,572 outputs
Outputs of similar age from Frontiers in immunology
#177
of 263 outputs
Altmetric has tracked 25,756,911 research outputs across all sources so far. This one is in the 34th percentile – i.e., 34% of other outputs scored the same or lower than it.
So far Altmetric has tracked 32,318 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.4. This one is in the 42nd percentile – i.e., 42% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 422,572 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 263 others from the same source and published within six weeks on either side of this one. This one is in the 28th percentile – i.e., 28% of its contemporaries scored the same or lower than it.