Roles of Kupffer Cell Polarization and Hepatic Stellate Cell Activation in Hepatic Inflammation and Fibrosis in NAFLD / 胃肠病学

ABSTRACT

Background:Kupffer cells and hepatic stellate cells(HSC)play important roles in the initiation and progression of hepatic inflammation and fibrosis in chronic liver injury. Aims:To investigate the roles of Kupffer cell polarization and HSC activation in the development of hepatic inflammation and fibrosis in progression of non-alcoholic fatty liver disease (NAFLD). Methods:C57BL/6 mice were fed with high fat(HF)diet and methionine-choline-deficient(MCD)diet to induce experimental non-alcoholic fatty liver(NAFL)and non-alcoholic steatohepatitis(NASH),respectively. Liver steatosis,inflammation and fibrosis were determined by histopathological examination through HE staining and Masson staining. Kupffer cell phenotypes and HSC activation were assessed by immunohistochemistry. Expressions of PPAR-γ as well as inflammation-and fibrosis-related genes were measured by real-time PCR. Results:F4/80-positive Kupffer cells, CD11c-positive M1 polarized macrophages and α-SMA-positive HSC were significantly increased in liver tissue of mice with HF diet-induced NAFL and MCD diet-induced NASH(P<0.05),and was more apparent in MCD diet-induced NASH (P<0.05). Expressions of TNF-α and TGF-β1 mRNA in liver tissue were significantly increased in both groups(P<0.05),whereas expressions of α-SMA and Col1 mRNA were significantly increased only in NASH(P<0.05). Hepatic PPAR-γ mRNA expression was significantly increased in NAFL(P<0.05)but significantly decreased in NASH(P<0.05). Conclusions:Hepatic Kupffer cells exists a sustained M1 polarization in the development of NAFLD. Activation of HSC appears in the early stage of NAFLD,and accelerates in the progression of NAFL to NASH. Polarization of Kupffer cells and activation of HSC initiate and promote hepatic inflammation and fibrosis in NAFLD.