Abstract
Purpose: Mac-2 binding protein (Mac-2bp) is a secreted glycoprotein known to be a ligand for Galectin-3, which is thought to regulate cell adhesion through interaction with Galectin-3. The association between blood levels of Mac-2bp and chronic liver diseases, including NASH, has been reported. In this study, we analyzed the relationship between serum Mac-2bp levels and pathological changes in a diet-induced mouse model of NASH.
Materials and Methods: Six-week-old male C57BL/6 mice were fed ad libitum a basal diet and a choline-deficient methionine-reduced high-fat amino acid diet (CDAHFD). Feeding periods of 2, 8, and 52 weeks were established. At the end of each period, blood and liver samples were collected for the various analyses.
Results and discussion: Serum Mac-2bp levels increased from 2 weeks in the CDAHFD group, and then showed further increases. In the liver, significant hepatocellular fatty change from 2 weeks, inflammation and fibrosis from 8 weeks, and neoplastic lesions with nodular masses at 52 weeks in the CDAHFD group. Liver fibrosis imaging by Sirius red staining of liver tissue, the amount of hydroxyproline in the liver, and the expression of fibrosis-related genes increased in a feeding period-dependent manner. These changes were correlated with serum Mac-2bp levels. Furthermore, some associations were also observed in the liver tumor marker α-fetoprotein, the size of nodular lesions, and serum Mac-2bp levels. Based on these results, serum Mac-2bp may be a potential biomarker for liver tumor as well as liver fibrosis in a mouse model of NASH.
