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Negative Regulators of JAK/STAT Signaling in Rheumatoid Arthritis and Osteoarthritis
- Source :
- International Journal of Molecular Sciences, International Journal of Molecular Sciences, Vol 18, Iss 3, p 484 (2017)
- Publication Year :
- 2017
- Publisher :
- MDPI AG, 2017.
-
Abstract
- Elevated levels of pro-inflammatory cytokines are generally thought to be responsible for driving the progression of synovial joint inflammation in rheumatoid arthritis (RA) and osteoarthritis (OA). These cytokines activate several signal transduction pathways, including the Janus kinase/Signal Transducers and Activators of Transcription (JAK/STAT), Stress-Activated/Mitogen-Activated Protein Kinase (SAPK/MAPK) and phosphatidylinositol-3-kinase/Akt/mechanistic target of rapamycin (PI3K/Akt/mTOR) pathways which regulate numerous cellular responses. However, cytokine gene expression, matrix metalloproteinase gene expression and aberrant immune cell and synoviocyte survival via reduced apoptosis are most critical in the context of inflammation characteristic of RA and OA. Negative regulation of JAK/STAT signaling is controlled by Suppressor of Cytokine Signaling (SOCS) proteins. SOCS is produced at lower levels in RA and OA. In addition, gaining further insight into the role played in RA and OA pathology by the inhibitors of the apoptosis protein family, cellular inhibitor of apoptosis protein-1, -2 (c-IAP1, c-IAP2), X (cross)-linked inhibitor of apoptosis protein (XIAP), protein inhibitor of activated STAT (PIAS), and survivin (human) as well as SOCS appears to be a worthy endeavor going forward.
- Subjects :
- 0301 basic medicine
chondrocytes
Review
Inhibitor of apoptosis
Catalysis
Inhibitor of Apoptosis Proteins
lcsh:Chemistry
Arthritis, Rheumatoid
Inorganic Chemistry
03 medical and health sciences
Osteoarthritis
Animals
Humans
Medicine
Protein inhibitor of activated STAT
SOCS3
Physical and Theoretical Chemistry
lcsh:QH301-705.5
Molecular Biology
Mechanistic target of rapamycin
Protein kinase B
Spectroscopy
PI3K/AKT/mTOR pathway
Janus Kinases
biology
business.industry
Organic Chemistry
apoptosis
General Medicine
Computer Science Applications
XIAP
STAT Transcription Factors
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
arthritis
Immunology
biology.protein
Cancer research
Cytokines
business
Janus kinase
Protein Binding
Signal Transduction
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....e9ae92a50f6fe06101062b5860f11248