A major focus of the Denhardt laboratory is the study of osteopontin (OPN). OPN is an O-glycosylated phosphoprotein that is synthesized in a variety of tissues and cells and secreted into body fluids. In the immune system, OPN is expressed by many different cell types, including macrophages, neutrophils, dendritic cells, NK cells, and T and B lymphocytes; it is up-regulated in response to injury and inflammation in every organ examined; for example, cardiac tissue, kidney, lung, bone, brain, the gastrointestinal tract, joints, liver, adipose tissue and most tumors. OPN has been identified as a biomarker for various types of cancers and inflammatory diseases. Excessive or dysregulated OPN expression has been linked to the pathogenesis of both autoimmune disorders such as multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, atherosclerosis and other inflammatory diseases including cardiovascular disease, chronic obstructive pulmonary disease, inflammatory bowel disease, liver disease and asthma. Although initially regarded as an RGD-containing adhesive bone matrix protein because of its presence in the extracellular matrix of mineralized tissues, it is now established as a soluble cytokine/hormone capable of stimulating signal transduction pathways in many different cell types.
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