• 中国精品科技期刊
  • 中国高校百佳科技期刊
  • 中国中文核心期刊
  • 中国科学引文数据库核心期刊
Advanced Search
CAI Yanfei, WAN Aini, CHEN Yun, JIN Jian. Anti-liver fibrosis activities of the extracellular domain of transforming growth factor beta type II receptor fusion protein in vivo[J]. Journal of China Pharmaceutical University, 2019, 50(2): 246-252. DOI: 10.11665/j.issn.1000-5048.20190217
Citation: CAI Yanfei, WAN Aini, CHEN Yun, JIN Jian. Anti-liver fibrosis activities of the extracellular domain of transforming growth factor beta type II receptor fusion protein in vivo[J]. Journal of China Pharmaceutical University, 2019, 50(2): 246-252. DOI: 10.11665/j.issn.1000-5048.20190217
shu

Anti-liver fibrosis activities of the extracellular domain of transforming growth factor beta type II receptor fusion protein in vivo

More Information
    Graphical Abstract
    • 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.
    • FullText(HTML)
    • References (15)
  • [1]
    Hernandezgea V,Friedman SL.Pathogenesis of liver fibrosis[J].Annu Rev Pathol Mech Dis,2011,6(1):425-456.
    [2]
    Huang YH,Shi MN,Zheng WD,et al.Therapeutic effect of interleukin-10 on CCl4-induced hepatic fibrosis in rats[J].World J Gastroenterol,2006,12(9):1386-1391.
    [3]
    Nakamuta M,Morizono S,Tsuruta S,et al.Remote delivery and expression of soluble type II TGF-beta receptor in muscle prevents hepatic fibrosis in rats[J].Int J Mol Med,2005,16(1):59-64.
    [4]
    Zhao LM,Wang SZ.Therapeutic applications of small molecule kinase inhibitors in liver fibrosis[J].J China Pharm Univ(中国药科大学学报),2018,49(2):147-157.
    [5]
    Bataller R,Brenner DA.Liver fibrosis[J].J Clin Invest,2005,115(2):209-218.
    [6]
    George J,Roulot D,Koteliansky VE,et al.In vivo inhibition of rat stellate cell activation by soluble transforming growth factor beta type II receptor:a potential new therapy for hepatic fibrosis[J].Proc Natl Acad Sci U S A,1999,96(22):12719-12724.
    [7]
    Wan AN,Miao YN,Peng L,et al.Binding and biologic characterization of recombinant human serum albumin-eTGFBR2 fusion protein expressed in CHO cells[J].Bioengineered,2017,8(5):600-612.
    [8]
    Kawaida K,Matsumoto K,Shimazu H,et al.Hepatocyte growth factor prevents acute renal failure of accelerates renal regeneration in mice[J].Proc Natl Acad Sci U S A,1994,91(10):4357-4361.
    [9]
    Kobayashi K. Summary of recombinant human serum albumin development[J].Biologicals,2006,34(1):55-59.
    [10]
    Wan AN, Xu DS, Liu KD, et al. Efficient expression of stable recombinant human insulin-like growth factor-1 fusion with human serum albumin in Chinese hamster ovary cells[J].Prep Biochem Biotechnol,2017,47(7):678-686.
    [11]
    Wan AN,Xu DD,Cai YF,et al.Anti-liver fibrosis activities of human insulin-like growth factor-1 in vitro[J].J China Pharm Univ(中国药科大学学报),2017,48(4):476-482.
    [12]
    Clichici S,Olteanu D,Filip A,et al.Beneficial effects of silymarin after the discontinuation of CCl4-induced liver fibrosis[J].J Med Food,2016,19(8):789-797.
    [13]
    Cao LB,Li B,Li ZJ,et al.The effect and mechanism of silymarin on liver fibrosis in mice[J].Chin Pharmacol Bull(中国药理学通报),2009,25(6):794-796.
    [14]
    Yata Y,Gotwals P,Koteliansky V,et al.Dose-dependent inhibition of hepatic fibrosis in mice by a TGF-β soluble receptor:implications for antifibrotic therapy[J].Hepatology,2002,35(5):1022-1030.
    [15]
    Castilla-Cortazar I,Garcia M,Muguerza B,et al.Hepatoprotective effects of insulin-like growth factor I in rats with carbon tetrachloride-induced cirrhosis[J].Gastroenterology,1997,113(5):1682-1691.
    • Related Articles

  • Related Articles

    [1]SUN Mingli, LIU Chen, WEI Yali, GAO Qian, LIU Qianying, WANG Xinghe. Bioequivalence of metformin hydrochloride sustained-release tablets under fed condition in healthy subjects[J]. Journal of China Pharmaceutical University, 2023, 54(1): 89-94. DOI: 10.11665/j.issn.1000-5048.20220922001
    [2]JI Shunli, SONG Fanfan, ZHENG Yang, DING Li. Simultaneous determination of amoxicillin and clavulanic acid by LC-MS/MS in human plasma and its application to a bioequivalence study[J]. Journal of China Pharmaceutical University, 2019, 50(6): 699-706. DOI: 10.11665/j.issn.1000-5048.20190610
    [3]XIAO Yuan-yuan, MA Peng-cheng, WANG Yan, REN Xin-yi, LIU Xiao-quan. Determination of 8′-hydroxy-dihydroergocryptine in human plasma by LC-MS/MS and its application to a bioequivalence evaluation[J]. Journal of China Pharmaceutical University, 2012, 43(2): 177-181.
    [4]Pharmacokinetics and Bioequivalence of Finasteride Tablets in Healthy Subjects[J]. Journal of China Pharmaceutical University, 2003, (6): 88-91.
    [5]Determination of Meloxicamin Human Plasma by HPLC and Evaluation of Its Bioequivalence Assessment[J]. Journal of China Pharmaceutical University, 2000, (4): 31-34.
    [6]Bioequivalence Study of the Two Kinds of Ofloxacin Tablets in Healthy Volunteers[J]. Journal of China Pharmaceutical University, 1998, (6): 433-436.
    [7]Bioequivalence of Doxofylline in Healthy Volunteers[J]. Journal of China Pharmaceutical University, 1998, (5): 33-35.
    [8]Pharmacokinetics and Bioequivalence of Sparfloxacin in Healthy Subject[J]. Journal of China Pharmaceutical University, 1998, (3): 75-77.
    [9]Studies on Ibuprofen Suspension and Its Bioequivalence in Healthy Volunteers[J]. Journal of China Pharmaceutical University, 1997, (3): 11-16.
    [10]Studies on Pharmacokinetics and Bioeqivalence of Aspirin Sustained-Release Pellets[J]. Journal of China Pharmaceutical University, 1993, (6): 334-337.

Catalog

    Get Citation
    PDF
    XML
    Article views (724) PDF downloads (875) Cited by()
    Turn off MathJax
    Article Contents
    Abstract
    References
    Related Articles

    Copyright © Journal of China Pharmaceutical University苏ICP备12050101号-2

    Address：24 Tongjia Lane, Nanjing City, Jiangsu Province （210009）Tel: 025-83271566E-mail: xuebao@cpu.edu.cn

    Supported by: Beijing Renhe Information Technology Co., Ltd.  Baidu Analytics

    Total visits：455477

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return