Anti-liver fibrosis activities of the extracellular domain of transforming growth factor beta type II receptor fusion protein in vivo
10.11665/j.issn.1000-5048.20190217
- VernacularTitle:转化生长因子βⅡ型受体胞外域融合蛋白的体内抗肝纤维化活性研究
- Author:
Yanfei CAI
;
Aini WAN
;
Yun CHEN
;
Jian JIN
- Publication Type:Journal Article
- Keywords:
extracellular domain of transforming growth factor beta type II receptor;
liver fibrosis;
human serum albumin fusion protein
- From:
Journal of China Pharmaceutical University
2019;50(2):246-252
- CountryChina
- Language:Chinese
-
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.
