High mobility group box 1 induces synoviocyte proliferation in rheumatoid arthritis by activating the signal transducer and activator transcription signal pathway

2010 ◽  
Vol 11 (2) ◽  
pp. 65-74 ◽  
Author(s):  
Hui-Fang Guo ◽  
Shu-Xia Liu ◽  
Yu-Jun Zhang ◽  
Qing-Juan Liu ◽  
Jun Hao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
High Mobility ◽  
Signal Pathway ◽  
High Mobility Group ◽  
Signal Transducer

High Mobility Group Box Chromosomal Protein-1 Induces Myofibroblast Differentiation and Extracellular Matrix Production via RAGE, p38, JNK and AP-1 Signaling Pathways in Nasal Fibroblasts

2021 ◽  
pp. 194589242199814
Author(s):  
Soo-Hyung Lee ◽  
Jae Hoon Cho ◽  
Joo-Hoo Park ◽  
Jung-Sun Cho ◽  
Heung-Man Lee
Keyword(s):  
Extracellular Matrix ◽  
Chronic Rhinosinusitis ◽  
Smooth Muscle Actin ◽  
High Mobility ◽  
Signal Pathway ◽  
High Mobility Group ◽  
Myofibroblast Differentiation ◽  
Chromosomal Protein ◽  
Protein Levels ◽  
Matrix Production

Background Chronic rhinosinusitis is involved in myofibroblast differentiation and extracellular matrix (ECM) accumulation. High mobility group box chromosomal protein 1 (HMGB-1) is known to stimulate lung fibroblast to produce ECM in lung fibrosis. The aim of this study was to investigate whether HMGB-1 induces myofibroblast differentiation and ECM production in nasal fibroblasts and to identify the signal pathway. Methods Human nasal fibroblasts were cultured. After stimulation with HMGB-1, expressions of α-smooth muscle actin (α-SMA) and fibronectin were determined by real-time PCR and western blot. Total collagen was measured by Sircol assay. To investigate signal pathway, various signal inhibitors and RAGE siRNA were used. Results HMGB-1 increased α-SMA and fibronectin in mRNA and protein levels. It also increased collagen production. RAGE siRNA inhibited HMGB-1-induced α-SMA and fibronectin, and production of collagen. Furthermore, the inhibitors of RAGE downstream molecules such as p38, JNK and AP-1 also blocked the HMGB-1-induced effects. Conclusions HMGB-1 induces myofibroblast differentiation and ECM production in nasal fibroblast, which is mediated by RAGE, p38, JNK and AP-1 signal pathway. These results suggest that HMGB-1 may play an important role in tissue remodeling during chronic rhinosinusitis progression.

scholarly journals The High-Mobility Group A1a/Signal Transducer and Activator of Transcription-3 Axis: An Achilles Heel for Hematopoietic Malignancies?

2008 ◽  
Vol 68 (24) ◽  
pp. 10121-10127 ◽  
Author(s):  
J. Hillion ◽  
S. Dhara ◽  
T. F. Sumter ◽  
M. Mukherjee ◽  
F. Di Cello ◽  
...  
Keyword(s):  
High Mobility ◽  
High Mobility Group ◽  
Signal Transducer ◽  
Hematopoietic Malignancies ◽  
Transcription 3

scholarly journals Influence of Polymorphism −308 G/A of the Tnf-α Gene on High Mobility Group Box-1 Protein in Rheumatoid and Spondylo-Arthritis Patients

2012 ◽  
Vol 10 (3) ◽  
pp. 405-412
Author(s):  
A. Bitto ◽  
F. Polito ◽  
G. Bagnato ◽  
R. Talotta ◽  
M. Atteritano ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Status ◽  
High Mobility ◽  
Gene Promoter ◽  
Human Tumor ◽  
High Mobility Group ◽  
University Hospital ◽  
Mrna Levels ◽  
Altered Expression ◽  
Tnf Α

Single nucleotide polymorphism (SNP) in the human Tumor Necrosis Factor-α(TNF-α) gene promoter, the −308 G/A variant, has been associated with increased TNF-α levels that may amplify the severity of rheumatoid arthritis (RA) and a poor responsiveness to TNF-α blockade therapy. High mobility group box protein (HMGB-1) is a pro-inflammatory cytokine that plays a pivotal role in the pathogenesis of RA and may be an original target of therapy. The aim of this study is to investigate whether the −308 G/A variant of the TNF-α gene is associated with altered expression of HMBG-1. A total of 110 consecutive patients with rheumatoid arthritis and spondylo-arthritis (ankylosing spondylitis, psoriatic arthritis and spondylitis associated with inflammatory bowel disease) referring to the Rheumatology Unit of Messina University Hospital were enrolled. Patients were genotyped for the −308 TNF-α gene promoter polymorphism. Clinical status was also assessed. HMGB-1 and TNF-α mRNA(Real Time PCR) from total blood and plasmatic HMGB-1 (Western Blot analysis) and TNF-α (ELISA) protein were also evaluated. Irrespective of the underlying disease, patients carrying the G/A genotype showed enhanced HMGB-1 and TNF-α mRNA levels and increased circulating concentration of the inflammatory cytokines when compared to patients with G/G genotype. The data suggest that subjects carrying the TNF-α −308G/A genotype have enhanced expression of HMGB-1 protein that may explain, at least in part, the increased severity of the disease.

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