[5] OPN mRNA expression was prominently higher in Kupffer cells, hepatic macrophages and stellate cells immediately after isolation from these intoxicated rats than in the cells from normal rats.[5] In heat-killed Propionibacterium acnes-treated rats, marked accumulation of macrophages developed in the liver later than 3 days after the intoxication and its extent became maximal between 5 and 7 days. In these rats, increased OPN mRNA expression in the liver occurred at 1 day with its peak at 3 days, and OPN mRNA expression in Kupffer cells and hepatic macrophages

isolated at 7 days was extremely increased.[6] Chemotaxis assay, using a cell culture chamber precoated with OPN, showed that OPN promoted migration of Kupffer cells isolated from normal rats in a dose-related manner.[5]

These results suggested that sOPN secreted by Kupffer cells and check details hepatic macrophages at inflammatory sites, contributed to macrophage recruitment into the sites of liver injury (Fig. 1). Furthermore, iOPN co-localized with the CD44-ERM complex may promote migration of macrophages.[26] NON-ALCOHOLIC FATTY LIVER disease is characterized by accumulation of excess hepatocellular triglyceride, which is associated with obesity and insulin resistance. Hepatic expressions Ribociclib datasheet of OPN and its receptor, CD44 mRNA, were significantly correlated with the grade of hepatic steatosis, plasma alanine aminotransferase level and hepatic insulin resistance in morbidly obese patients.[27] NASH, a subset of NAFLD, shows hepatic necroinflammatory changes and often progresses Molecular motor to liver fibrosis and

cirrhosis. Hepatic OPN mRNA expression was significantly increased in patients with NAFLD than in controls with normal liver, while the expression was significantly decreased in those with NASH compared to those without NASH.[28] Among patients with NASH, immunohistochemical expression of OPN was significantly greater in the liver with advanced fibrosis than in that with early fibrosis.[10] Plasma OPN level was also significantly higher in patients with NASH with advanced fibrosis than in those with early fibrosis.[10] In obese mice fed a high-fat diet, OPN deficiency protected against hepatic steatosis[29] and inflammation.[29, 30] Decreased steatosis in OPN–/– mice fed a high-fat diet was paralleled by improved whole-body insulin sensitivity, mainly due to reduction in hepatic insulin resistance and gluconeogenesis. In addition, hepatocyte ballooning, portal leukocyte infiltration and hepatic macrophage accumulation were attenuated by genetic OPN deficiency.[29] Antibody-mediated OPN neutralization also inhibited accumulation of hepatic macrophages and insulin resistance, induced by a high-fat diet in mice (Fig. 2).