Targeting osteopontin to treat primary sclerosing cholangitis

Primary sclerosing cholangitis is a chronic cholestatic liver disease for which no pharmacological treatment options are available. It is an immune-mediated disease and macrophages have been implicated in disease pathogenesis. However, which specific macrophage populations contribute to disease, and how we can apply this as therapeutic strategy is still unclear.

Recent studies have shown that fibrous tissue is characterized by osteopontin-positive macrophages, including in patients with primary sclerosing cholangitis. Experimental models indicate that intracellular osteopontin in macrophages confers protection, while secreted osteopontin contributes to disease. Serum osteopontin is increased in different liver diseases, including primary sclerosing cholangitis, and might thus serve as therapeutic target.

Although several studies report on the role of osteopontin in liver disease, only a minority of the studies have focused on isoform-specific functions, and the importance of the cellular source of secreted osteopontin. Future studies investigating these aspects, and how this can be translated to therapies for primary sclerosing cholangitis, and other chronic liver diseases, are required.