Functions Of Periostin In Bile Duct Ligation And CCl₄-induced Mouse Liver Fibrosis

Fibrosis is a universal pathological process in most human chronic liver diseases. During liver injury, parenchyma cells undergo necrosis or apoptosis and then marcophages are recruited to the injuried area. Hepatic stellate cells are activated and secret excessive extracellular matrix into the space of Disse. When the injury persists, the disrupted homeostasis between the synthesis and degradation of extracellular matrix results in liver fibrosis. Periostin is an extracellular matrix protein involved in tumorigenesis and metastasis. Periostin has been reported to participate in a variety of tissue fibrosis and is highly expressed in human chronic liver diseases. In myocardial and lung fibrosis, the deletion of Periostin displayed reduced fibrosis in mice, but whether Periostin functions in liver fibrosis or not remains unclear. Our study deciphers the role of Periostin in liver fibrosis. First, by employing two well-established models of liver fibrosis:toxic CCl4model and billiary BDL model, we discovered that Periostin was increased in mice with8weeks CCl4treatment or7and21days BDL administration. In CCl4-induced fibrosis model, wildtype mice showed more severe chronic liver injury and elevated fibrosis compared to periostin-/-mice. Periostin was mainly expressed in injuried liver portal area and co-localized with Collagen I and a-SMA expressed by myofibroblasts which are derived from activated HSCs. We could not detect the expression of Periostin in isolated primary hepatocytes and hepatic stellate cells as well as in hepatocyte with LPS stimulation; however, Periostin expression is strongly induced in hepatic stellate cells with TGF-(31stimulation. The mRNA level of TGF-β significantly decreased in periostin-/-mice with8weeks CCl4administration. Taken together, our study suggested that Periostin plays a role in liver fibrosis. Kuppfer cells secret inflammatory cytokines like TGF-P to activate hepatic stellate cells, then activated hepatic stellate cells secret Periostin which may mediate the response to CCl4-induced liver fibrosis by modulating TGF-β signaling.