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Down-regulating peroxisome proliferator-activated receptor-gamma coactivator-1beta alleviates the proinflammatory effect of rheumatoid arthritis fibroblast-like synoviocytes through inhibiting…

Overview of attention for article published in Arthritis Research & Therapy, October 2014
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Title
Down-regulating peroxisome proliferator-activated receptor-gamma coactivator-1beta alleviates the proinflammatory effect of rheumatoid arthritis fibroblast-like synoviocytes through inhibiting extracellular signal-regulated kinase, p38 and nuclear factor-kappaB activation
Published in
Arthritis Research & Therapy, October 2014
DOI 10.1186/s13075-014-0472-6
Pubmed ID
Authors

Jing-Jing Zhou, Jian-Da Ma, Ying-Qian Mo, Dong-Hui Zheng, Le-Feng Chen, Xiu-Ning Wei, Lie Dai

Abstract

IntroductionRheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint destruction and disability. Peroxisome proliferator-activated receptor-gamma coactivator-1beta (PGC-1ß) is a transcriptional coactivator that plays important roles in regulating multiple aspects of energy metabolism and cytokine signaling pathways. PGC-1ß overexpression leads to the attenuation of macrophage-mediated inflammation. In this study, we aimed to determine the expression of PGC-1ß in RA synovium and fibroblast-like synoviocytes (FLS), and explore the mechanisms of PGC-1ß on both the proinflammatory effects and apoptosis in RA-FLS.MethodsSynovium was obtained from 31 patients with active RA, as well as 13 osteoarthritis (OA) and 10 orthopedic arthropathies (Orth.A) as ¿less inflamed¿ disease controls. FLS were then isolated and cultured. Synovial PGC-1ß expression was determined by immunohistochemistry staining, while FLS PGC-1ß expression was detected by immunofluorescence staining, quantitative real-time PCR (qPCR) assay and western blot. PGC-1ß was depleted by lentivirus sh-RNA, and up-regulated by pcDNA3.1- PGC-1ß. The expression of proinflammatory cytokines, matrix metalloproteinases and receptor activator of nuclear factor-kappaB ligand was analyzed by qPCR, cytometric bead array and western blot. The expression of mitogen-activated protein kinases and nuclear factor-kappaB (NF-¿B) was determined by qPCR and western blot. Besides, cell apoptosis was examined using flow cytometry. The interaction between PGC-1ß and NF-¿B was performed by dual-luciferase reporter gene assays.Results(A) Synovial PGC-1ß was over-expressed in RA patients compared with OA or Orth.A patients. (B) PGC-1ß expression significantly increased in RA-FLS compared with OA-FLS. (C) PGC-1ß mediated the expression of proinflammatory cytokines and apoptosis through extracellular signal-regulated kinase (ERK), p38 and NF-¿B in RA-FLS. (D) PGC-1ß mediated NF-¿B transcription in RA-FLS, but did not affect ERK and p38.ConclusionThe results indicate that PGC-1ß may play important roles in the proinflammatory effects and apoptosis of RA-FLS.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 6%
Unknown 15 94%

Demographic breakdown

Readers by professional status Count As %
Researcher 4 25%
Student > Postgraduate 3 19%
Student > Ph. D. Student 3 19%
Other 1 6%
Student > Doctoral Student 1 6%
Other 2 13%
Unknown 2 13%
Readers by discipline Count As %
Medicine and Dentistry 4 25%
Immunology and Microbiology 3 19%
Pharmacology, Toxicology and Pharmaceutical Science 1 6%
Biochemistry, Genetics and Molecular Biology 1 6%
Agricultural and Biological Sciences 1 6%
Other 3 19%
Unknown 3 19%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 22 November 2014.
All research outputs
#3,676,565
of 4,535,990 outputs
Outputs from Arthritis Research & Therapy
#947
of 1,090 outputs
Outputs of similar age
#110,298
of 141,099 outputs
Outputs of similar age from Arthritis Research & Therapy
#46
of 50 outputs
Altmetric has tracked 4,535,990 research outputs across all sources so far. This one is in the 3rd percentile – i.e., 3% of other outputs scored the same or lower than it.
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