Pioglitazone suppresses inflammation and fibrosis in nonalcoholic fatty liver disease by down-regulating PDGF and TIMP-2: Evidence from in vitro study

• Published in: Cancer biomarkers : section A of Disease markers Vol. 20; no. 4; pp. 411 - 415
• Main Authors: Deng, Wen, Meng, Zimin, Sun, Aitao, Yang, Zhihong
• Format: Journal Article
• Language: English
• Published: Netherlands IOS Press BV 06.12.2017
• Subjects: Diet; Enzyme-linked immunosorbent assay; Fatty liver; Fibrosis; Hafnium; High fat diet; Histology; Inflammation; Liver; Liver diseases; Metalloproteinase; Mice; Peroxisome proliferator-activated receptors; Pharmacology; Pioglitazone; Platelet-derived growth factor; Rodents; Steatosis; Tissue inhibitor of metalloproteinase 2; NAFLD; TIMP-2; pioglitazone; hepatic fibrosis; PDGF
• ISSN: 1574-0153; 1875-8592
• DOI: 10.3233/CBM-170157

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing worldwide. Pioglitazone is a pharmacologic agonist of peroxisome proliferators-activated receptor-γ (PPAR-γ) that was reported to ameliorate hepatic steatosis and inflammatory changes. We aimed to evaluate the effects of pioglitazone in NAFLD and investigate the underlying mechanism by testing platelet derived growth factor (PDGF) and tissue inhibitory of metalloproteinase-2 (TIMP-2). A total of C57BL/6 wild-type mice were randomized to three groups, control group (NC, n= 60), high-fat control group (HF, n= 60), and pioglitazone treatment group (L,n= 60). Mice were administrated with high-fat diet to construct NAFLD model. Enzyme-linked immunosorbent assay (ELISA) was used to measure protein expression of PDGF and TIMP-2. Liver histology samples were stained with hematoxylin and eosin (H&E). Upon pioglitazone treatment, the PDGF and TIMP-2 expression levels were decreased compared with high-fat diet-fed mice devoid of drug stimulation. Analysis of liver histology showed pioglitazone treatment could reduce steatosis and inflammatory changes, which was helpful to inhibit hepatic fibrosis in NAFLD mice. The study showed pioglitazone might exert an inhibitory effect on hepatic inflammation and fibrosis in NAFLD. Moreover, this study provided novel evidence for the promising clinical application of pioglitazone in intervening NAFLD.