[Role of hypoxia-inducible factor in the pathogenesis of rheumatoid arthritis].

Abstract

Rheumatoid arthritis (RA) is a destructive chronic autoimmune disease characterized by synovium inflammation, cartilage destruction, bone erosion and the presence of autoantibodies. Hypoxia is a prominent micro-environmental feature in a range of disorders including RA. A combination of increased oxygen consumptionby inflamed resident cells and infiltrating immune cells along with a disrupted blood supply due to vascular dysfunction contribute to tissue hypoxia in RA. Hypoxia in turn regulates a number of key signaling pathways that help adaptation. The primary signaling pathway activated by hypoxia is the hypoxia-inducible factor (HIF) pathway. It has been shown that HIFs are highly expressed in the synovium of RA. HIFs mediate the pathogenesis of RA through inducing inflammation, angiogenesis, cell migration, and cartilage destruction, and inhibiting the apoptosis of synovial cells and inflammatory cells. HIF expressed in RA can be regulated in both oxygen-dependent and independent fashions, like inflammatory cytokines, leading to the aggravation of this disease. Considering the vital role of HIF in the pathogenesis of RA, we reviewed the new advances about hypoxia and RA. In this review, we firstly discussed the hypoxia-inducible factor and its regulation, and then, the pathologic role of hypoxia in RA, mainly elucidating the role of hypoxia in synovitis and cartilage destruction and immune cells. Finally, we provided evidence about the potential therapeutic target for treating RA.

• Authors: R H Yu, J X Zhao, X Y Liu
• Journal: Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences (Beijing Da Xue Xue Bao Yi Xue Ban) Vol. 48 Issue 6 Pg. 1095-1099 (12 18 2016) ISSN: 1671-167X [Print] China
• PMID: 27987521 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ARNT2 protein, human
• Apoptosis Regulatory Proteins
• Basic Helix-Loop-Helix Transcription Factors
• HIF3A protein, human
• Hypoxia-Inducible Factor 1
• Repressor Proteins
• Aryl Hydrocarbon Receptor Nuclear Translocator
• endothelial PAS domain-containing protein 1

Topics

• Apoptosis (genetics)
• Apoptosis Regulatory Proteins
• Arthritis, Rheumatoid (genetics, physiopathology)
• Aryl Hydrocarbon Receptor Nuclear Translocator (immunology)
• Basic Helix-Loop-Helix Transcription Factors (immunology)
• Cartilage (immunology, pathology, physiopathology)
• Cell Movement (genetics, immunology)
• Humans
• Hypoxia (genetics, immunology, physiopathology)
• Hypoxia-Inducible Factor 1 (immunology)
• Inflammation (genetics, immunology)
• Neovascularization, Pathologic (genetics, immunology)
• Repressor Proteins
• Synovial Membrane (immunology, pathology, physiopathology)