S100A4 Gene is Crucial for Methionine-Choline-Deficient Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice

• Published in: Yonsei medical journal 2018, 59(9), , pp.1064-1071
• Main Authors: Zhang, Yin Hua, Ma, De Qiang, Ding, De Ping, Li, Juan, Chen, Lin Li, Ao, Kang Jian, Tian, You You
• Format: Article
• Language: English
• Subjects: Alanine Transaminase - blood; Animals; Apoptosis; Aspartate Aminotransferases - blood; Aspartate Aminotransferases - metabolism; Choline Deficiency - blood; Choline Deficiency - metabolism; Diet - adverse effects; Inflammation - metabolism; Interleukin-1beta; Liver - metabolism; Liver Cirrhosis - pathology; Male; Methionine - blood; Methionine - deficiency; Mice; Mice, Inbred C57BL; Mice, Knockout; Non-alcoholic Fatty Liver Disease - blood; Non-alcoholic Fatty Liver Disease - pathology; Original; S100 Calcium-Binding Protein A4; Triglycerides - metabolism; Tumor Necrosis Factor-alpha - metabolism; 의학일반
• ISSN: 0513-5796; 1976-2437
• DOI: 10.3349/ymj.2018.59.9.1064

To explore the influence of S100 calcium binding protein A4 (S100A4) knockout (KO) on methionine-choline-deficient (MCD) diet-induced non-alcoholic fatty liver disease (NAFLD) in mice. S100A4 KO mice (n=20) and their wild-type (WT) counterparts (n=20) were randomly divided into KO/MCD, Ko/methionine-choline-sufficient (MCS), WT/MCD, and WT/MCS groups. After 8 weeks of feeding, blood lipid and liver function-related indexes were measured. HE, Oil Red O, and Masson stainings were used to observe the changes of liver histopathology. Additionally, expressions of S100A4 and proinflammatory and profibrogenic cytokines were detected by qRT-PCR and Western blot, while hepatocyte apoptosis was revealed by TUNEL staining. Serum levels of aminotransferase, aspartate aminotransferase, triglyceride, and total cholesterol in mice were increased after 8-week MCD feeding, and hepatocytes performed varying balloon-like changes with increased inflammatory cell infiltration and collagen fibers; however, these effects were improved in mice of KO/MCD group. Meanwhile, total NAFLD activity scores and fibrosis were lower compared to WT+MCD group. Compared to WT/MCS group, S100A4 expression in liver tissue of WT/MCD group was enhanced. The expression of proinflammatory (TNF-α, IL-1β, IL-6) and profibrogenic cytokines (TGF-β1, COL1A1, α-SMA) in MCD-induced NAFLD mice were increased, as well as apoptotic index (AI). For MCD group, the expressions of proinflammatory and profibrogenic cytokines and AI in KO mice were lower than those of WT mice. S100A4 was detected to be upregulated in NAFLD, while S100A4 KO alleviated liver fibrosis and inflammation, in addition to inhibiting hepatocyte apoptosis.