ABSTRACT
@#This study is performed to analyze the anti-liver fibrosis effect of the fusion protein of human serum albumin and extracellular domain of transforming growth factor beta type II receptor(eTGFBR2)in vivo to looking for the more stable anti-liver fibrosis drug. The mice model of liver fibrosis was constructed by CCl4 induction and the following groups are included in the study: the control group, CCl4 model group, the positive control group, eTGFBR2 treatment group, HSA-eTGFBR2 treatment group, and HSA group. Hematoxylin eosin staining, serum liver function index detection, and western blot are used to identify the anti-liver fibrosis activities. The results showed that: (1)CCl4 caused liver structure disorder, hepatocellular necrosis, collagen fibers proliferation, and induced liver fibrosis at last; (2)HSA-eTGFBR2 and its monomer drug improved the symptoms of liver fibrosis significantly, as well as reduced the damage of liver cells and collagen deposition, and recovered the liver basic structure to normal. Both of HSA-eTGFBR2 and its monomer drug improved liver function and reduced the expression level of liver fibrosis marker α-SMA and COL I. Moreover, the anti-liver fibrosis effect of the fusion protein is comparable to the monomer drug. In contrast, the albumin had no effect on therapeutic effect; (3)Reducing the injection frequency of HSA-eTGFBR2 achieved the comparable effects to the monomer drug with the normal injection frequency. In summary, the fusion protein HSA-eTGFBR2 has good anti-liver fibrosis effect. In addition, reducing the injection frequency of the fusion protein could also achieve the comparable treatment with the monomer drug, indicating that the fusion protein is stable and has longer half-lives and then a relatively positive application prospect in future.
ABSTRACT
This study was focus on investigating the anti-liver fibrosis effects of insulin-like growth factor-1 (IGF-1) in vitro.The effects of IGF-1 on human liver L-02 cell viability and cell cycle were observed.CC14-induced L-02 cell injury was set up to detect the anti-apoptotic activity of insulin-like growth factor-1 (IGF-1).Transforming growth factor β1 (TGF-β1) induced hepatic stellate cell line (HSC-T6) were used as a liver fibrosis model in vitro to analyze the effects of IGF-1 on the expression of liver fibrosis proteins and intracellular TGF-β1/Smad signaling pathway in HSC-T6 cells.The results showed that IGF-1 could relieve the growth inhibition effects of TGF-β1 on L-02 cells,increase the viability of L-02 cells injured by CCl4,decrease the expression of liver fibrosis proteins,and inhibit the TGF-β1/Smad signaling pathway by inhibiting the phosphorylation of Smad3.Our study suggested that IGF-1 exerted anti-liver fibrosis effects by stimulating L-02 cells proliferation,reducing cell damage and inhibiting ECM accumulation via interfering TGF-β1/Smad signaling pathway.
ABSTRACT
Liver fibrosis is a common chronic liver disease, which is a stress response process of liver cells affected by one or more pathogenies for long term or repeatedly. During the fibrosis process, massive accumulated extracellular matrix can form scar tissue, which results in liver dysfunction or failure and seriously endangers the health of people. According to many independent reports, stem cell therapy can facilitate the alleviation of liver fibrosis. During the stem cell therapy, stem cells migrate to the injury site of liver and alleviate the liver fibrosis by improving the microenvironment of the scar area via paracrine way. This article reviews the formation, treatment, and stem cell therapy of liver fibrosis.