Abstract
Hepatic fibrogenesis involves the activation of hepatic stellate cells (HSCs), which synthesize excess extracellular matrix and contribute to the development of liver fibrosis. In a prior study we tested the effect of combined treatment with taurine, epigallocatechin gallate and genistein on the development of alcohol-induced liver fibrosis in vitro. In this study, the biological activity of the combination of these molecules was assessed by measuring its effect on cell proliferation, fibrosis-related gene expression, and proteomic expression profiling in the activated HSC cell line, HSC-T6. HSC-T6 cells were incubated with different concentrations of the drug combination taurine, epigallocatechin gallate and genistein. Cell proliferation was evaluated by MTT assay. Transforming growth factor β1 (TGF-β1), collagen type I (Col-I), matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) mRNA were analyzed by semi-quantitative reverse-transcription PCR. Proteomic profiling of HSC-T6 cells was also performed by SELDI-TOF-MS. Combined drug treatment significantly inhibited cell proliferation and TGF-β1, Col-I, TIMP-1 and TIMP-2 mRNA expression in activated HSC-T6 cells, while the expression of MMP-2 mRNA increased. A total of 176 protein m/z peaks were identified. The intensities of 10 protein peaks were downregulated and two protein peaks were upregulated in HSC-T6 cells after combined drug treatment. In conclusion, combined drug treatment with taurine, epigallocatechin gallate and genistein can inhibit HSC proliferation, and impact fibrosis-related gene and protein expression. The antifibrotic effects of this drug combination may be due to its effects on the expression of fibrogenic genes.
Highlights
Liver fibrosis is a reversible wound-healing response to either acute or chronic cellular injury that reflects a balance between liver repair and scar formation [1]
The anti-proliferative effect of combined taurine, epigallocatechin gallate (EGCG) and genistein treatment in hepatic stellate cells (HSCs)-T6 cells was determined by measuring cell viability using MTT assay
A key discovery in understanding the mechanisms underlying hepatic fibrosis has been the identification of HSCs as the primary effector cell in the pathogenic disease process, as they orchestrate the deposition of extra-cellular matrix (ECM) in the normal and fibrotic liver [17]
Summary
Liver fibrosis is a reversible wound-healing response to either acute or chronic cellular injury that reflects a balance between liver repair and scar formation [1]. Research into the identification of more effective therapies to treat hepatic fibrosis with fewer side effects is warranted In this regard, combination therapies with multiple drugs are thought to be superior to monotherapy because of their additive or synergistic effects and relief from side effects [9,10]. We reported that combined therapy with taurine, EGCG and genistein had an obvious protective effect against alcohol-induced liver fibrosis in rats by suppressing the serum levels of fibrosis markers and hepatic hydroxyproline content, as well as inhibiting hepatic collagen deposition and protein expression of B-cell lymphoma 2, α-smooth muscle actin, TGF-β1, and others against decapentaplegic homolog 3 (SMAD-3) [16]. We evaluated the mechanistic effect of combined taurine, EGCG and genistein therapy on hepatic fibrosis using an in vitro HSC model. We believe this research will provide new insights into the use of combined therapies to treat hepatic fibrosis
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