ITRAQ-based proteomic analysis of combination therapy with taurine, epigallocatechin gallate, and genistein on carbon tetrachloride-induced liver fibrosis in rats

Abstract

Combination therapy with taurine, epigallocatechin gallate, and genistein was effective in alleviating the progression of liver fibrosis in our previous study. To better understand the anti-fibrotic mechanisms of combination therapy, an iTRAQ-based proteomics approach was used to study the expression profiles of proteins in carbon tetrachloride-induced liver fibrosis rats following combination therapy. The anti-fibrotic effects of combination therapy were assessed directly by liver histology, and indirectly by measurement of serum biochemical markers and antioxidant enzymes. The results showed that combination therapy could significantly improve the liver function, as indicated by decreasing levels of alanine aminotransferase (ALT), aspartate transaminase (AST), transforming growth factor-β1 (TGF-β1), and collagen I, increasing levels of total antioxidative capacity (T-AOC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px), and reducing the pathological tissue damage. A total of 89 differential expressed proteins in response to combination therapy were identified by iTRAQ, which were interacted with each other and involved in different biological processes and pathways. Four differentially expressed proteins (Tpi1, Txn1, Fgb, and F7) involved in antioxidant defense system, glycolysis pathway and coagulation cascade pathway were validated by enzyme-linked immunosorbent assay. Our work provided valuable insights into the molecular mechanism of combination therapy against liver fibrosis, and the identified targets may be useful for treatment of liver fibrosis in future.