Effect of a porcine liver peptide extract on TGF-β induced activation of hepatic stellate cells

Liver fibrosis could lead to cirrhosis, liver failure, and even liver cancer. Activation of hepatic stellate cells (HSCs) is one of the major mechanisms of liver fibrogenesis. Inhibition of HSCs activation may provide promising therapies against liver fibrogenesis. Porcine liver peptide extracts were shown to have anti-fibrotic effect in clinical studies. The present study investigated the anti-fibrotic mechanism of a specifically prepared porcine liver peptide extract (PPE) through its effect on liver stellate cells LX-2. Transforming growth factor beta 1 (TGF-beta 1) was used to activate HSCs LX-2 cells. LX-2 cell proliferation was analyzed by 3-( 4,5-dimethylthiazol 2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay. Effect of PPE on the mRNA expression of matrix metallproteinase-2 (MMP-2) and tissue inhibitors of metalloproteinase-1 (TIMP-1) genes, and protein levels of type I and type III collagens in the presence or absence of TGF-beta 1, were measured by reverse transcription polymerase chain reaction (RT-PCR) and western blotting analysis, respectively. In the presence of TGF-beta 1, LX-2 cells significantly proliferated, which could be reversed to basal level in the presence of PPE. Gene expression of MMP-2 and TIMP-1 and protein expression of type I and III collagen were increased in the presence of TGF-beta 1, but their expressions were reduced when the cells were co-treated with PPE. PPE alone did not affect the cell proliferation and the expression of the relevant genes and proteins. The results showed that PPE might have a beneficial effect reducing liver fibrosis through prevention of human HSCs activation and proliferation stimulated by TGF-beta 1.