Relationship between PTGS2 and Pathological Development of Liver Fibrosis in Rats and Regulation of the Epithelial Mesenchymal Transition in Liver Tissue

Abstract

Backgrounds: Liver fibrosis (LF) is the pathological basis of various chronic liver diseases. An in-depth understanding of the pathologic alterations leading to LF is of great significance for the future diagnosis and treatment of LF. The objective of this study was to investigate the role of prostaglandin-endoperoxide synthase 2 (PTGS2) in LF and to provide a potential new target for diagnosis and treatment of LF. Methods: Twelve Specific Pathogen Free (SPF)-grade SD rats were randomized into four equal groups. One group was left untreated as the control group. The other three groups were subjected to LF modeling. LF was induced by intraperitoneal injection of a carbon tetrachloride/olive oil mixture twice weekly for 8 weeks. Three groups of LF model rats were then selected. One group was injected with lentiviral vector inhibiting PTGS2 expression (PTGS2 group), one group was injected with PTGS2 empty vector (blank group), and one group was injected with saline (model group). After 24 hours, the liver function of each group was measured, and the body weight and liver weight were obtained to calculate the liver index. Liver tissues were taken for hematoxylin-eosin (HE) staining and histopathologic examination, and the expressions of transforming growth factor-β (TGF-β), α-smooth muscle actin (α-SMA), E-cadherin and N-cadherin were measured. Results: A large number of steatosis and inflammatory cell infiltration, interlobular connective tissue hyperplasia and fibrous septum formation were observed in the liver tissues of rats in the model and blank groups, which were significantly improved in the PTGS2 group. Alanine transaminase (ALT) in the PTGS2 group was significantly lower than in the model and blank groups, but significantly higher than in the control group (p < 0.05). There was no difference in liver index between the PTGS2 and control groups, both of which were lower than the model and blank groups (p < 0.05). TGF-β and α-SMA mRNAs were higher in the PTGS2 group than in the control group and lower than in the model and blank groups (p < 0.05). E-cadherin was decreased, while N-cadherin was increased (p < 0.05), in both the model and blank groups compared to the control and PTGS2 groups. Conclusion: Blocking PTGS2 expression ameliorated hepatic damage and reversed epithelial mesenchymal transition (EMT) in LF rats.