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In recent years, an increasing number of reports have shown the involvement of osteopontin (OPN), a pleiotropic cytokine and an important component of the extracellular matrix (ECM), in the pathogenesis of liver injury and the development of fibrosis.1 ,2 OPN is also frequently overexpressed in hepatocellular carcinoma (HCC), where it modulates HCC growth, invasion and metastasis,2 and in cholangiocarcinoma, where its expression bears prognostic significance. Previous studies3 have shown that in injured livers OPN is expressed by hepatic stellate cells (HSC) and upregulates collagen I production. Interestingly, in HSC, OPN expression appears to be downstream of SOX9, a Hedgehog- and Notch-controlled transcription factor that is expressed also in biliary cells and hepatic progenitor cells (HPC)/hepatocytes committed to the biliary fate.4–6 In this issue of Gut, two papers investigate the role of OPN in HPC-driven ductular reaction (DR) in relation to the progression of liver fibrosis.7 ,8
DR, a histological lesion present in most chronic liver diseases, is a dynamic, multicellular complex characterised by the presence of ‘reactive’ ductular epithelial cells, arranged in irregular strings along the margins of the portal tract in close contact with mesenchymal, inflammatory and endothelial cells. Reactive ductular cells acquire novel functions including the secretion of cytokines, chemokines, growth factors and angiogenic factors, enabling them to establish intense paracrine communications with …
Contributors All authors were responsible for drafting and editing of the commentary.
Funding NIH Grant DK079005 and DK034989 Silvio O. Conte Digestive Diseases Research Core Centers to MS, projects CARIPLO 2011-0470 and PRIN 2009ARYX4T_005 to MS and EA. Telethon (grant #GGP09189) and Progetto di Ricerca Ateneo 2011 (grant #CPD113799/11) to LF.
Competing interests None.
Provenance and peer review Commissioned; internally peer reviewed.
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