Rachel W. Li
Australian National University Medical School, Australia
Title: Heparanase may have a key role in the regulation of inflammatory mediators in Rheumatoid Arthritis
Biography
Biography: Rachel W. Li
Abstract
Heparanase is the only known mammalian endoglycosidase capable of degrading the heparan sulfate (HS) glycosaminoglycan, both in extracellular space and within the cell. HS is reported to control inflammatory responses at multiple levels, including the sequestration of cytokines/chemokines in the extracellular space, the modulation of the leukocyte interaction with the endothelium and ECM, and the initiation of innate immune responses. We have reported heparanase expression in synovium of rheumatoid arthritis (RA) patients, and this new finding may offer a new insight of the potential regulatory role of heparanase in the disease activity of RA.However, the precise mode of action by heparanase in inflammatory reactions of RA remains largely unknown. The aim of this project was to examine the heparanase activity, its expression and correlation with the inflammatory mediatory and angiogenic gene expression in plasma and synovium of RA patients, with an ultimate goal of developing heparanase as a potential predictor of RA progression and a new therapeutic target. We have found that a highly significant increase of heparanase activity and expression in synovial fluid and synovial tissue of RA patients, and an increase of the heparanase activity positively correlate with the inflammatory and angiogenic gene expression. We also have some evidence to support a postulation that the involvement of heparanase in gene regulation in the development of pannus in RA may be reflected in a patient’s blood, thus heparanase can be a potential predictor of RA progression and a novel therapeutic target.