Hypoxia-Inducible Factor (HIF) as a Target for Novel Therapies in Rheumatoid Arthritis

Susan Hua, Thilani H Dias, Susan Hua, Thilani H Dias

Abstract

Hypoxia is an important micro-environmental characteristic of rheumatoid arthritis (RA). Hypoxia-inducible factors (HIF) are key transcriptional factors that are highly expressed in RA synovium to regulate the adaptive responses to this hypoxic milieu. Accumulating evidence supports hypoxia and HIFs in regulating a number of important pathophysiological characteristics of RA, including synovial inflammation, angiogenesis, and cartilage destruction. Experimental and clinical data have confirmed the upregulation of both HIF-1α and HIF-2α in RA. This review will focus on the differential expression of HIFs within the synovial joint and its functional behavior in different cell types to regulate RA progression. Potential development of new therapeutic strategies targeting HIF-regulated pathways at sites of disease in RA will also be addressed.

Keywords: angiogenesis; cartilage degradation; hypoxia; hypoxia-inducible factor; inflammation; rheumatoid arthritis; synovitis; targeted therapy.

Figures

Figure 1
Figure 1
Role of hypoxia-regulated HIF-α transcription factors in inflammation and destruction of the RA joint. HIF-α can directly modulate the expression of mediators that are involved in synovitis, angiogenesis, cartilage destruction, and bone erosion. This can also influence the composition of the cellular infiltrate in the synovial tissue and perpetuate the progression of disease.

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