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Pentoxifylline inhibits liver fibrosis via hedgehog signaling pathway

  • Hui Li (李 慧)
  • Juan Hua (华 娟)
  • Chun-xia Guo (郭春霞)
  • Wei-xian Wang (王伟仙)
  • Bao-ju Wang (王宝菊)
  • Dong-liang Yang (杨东亮)
  • Ping Wei (魏 屏)Email author
  • Yin-ping Lu (卢银平)Email author
Article

Summary

Infection of schistosomiasis japonica may eventually lead to liver fibrosis, and no effective antifibrotic therapies are available but liver transplantation. Hedgehog (HH) signaling pathway has been involved in the process and is a promising target for treating liver fibrosis. This study aimed to explore the effects of pentoxifylline (PTX) on liver fibrosis induced by schistosoma japonicum infection by inhibiting the HH signaling pathway. Phorbol12-myristate13-acetate (PMA) was used to induce human acute mononuclear leukemia cells THP-1 to differentiate into macrophages. The THP-1-derived macrophages were stimulated by soluble egg antigen (SEA), and the culture supernatants were collected for detection of activation of macrophages. Cell Counting Kit-8 (CCK-8) was used to detect the cytotoxicity of the culture supernatant and PTX on the LX-2 cells. The LX-2 cells were administered with activated culture supernatant from macrophages and(or) PTX to detect the transforming growth factor-β gene expression. The mRNA expression of shh and gli-1, key parts in HH signaling pathway, was detected. The mRNA expression of shh and gli-1 was increased in LX-2 cells treated with activated macrophages-derived culture supernatant, suggesting HH signaling pathway may play a key role in the activation process of hepatic stellate cells (HSCs). The expression of these genes decreased in LX-2 cells co-cultured with both activated macrophages-derived culture supernatant and PTX, indicating PTX could suppress the activation process of HSCs. In conclusion, these data provide evidence that PTX prevents liver fibrogenesis in vitro by the suppression of HH signaling pathway.

Key words

pentoxifylline schistosomiasis japonica hedgehog signaling pathway macrophages hepatic stellate cells 

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Copyright information

© Huazhong University of Science and Technology and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Hui Li (李 慧)
    • 1
  • Juan Hua (华 娟)
    • 1
  • Chun-xia Guo (郭春霞)
    • 1
  • Wei-xian Wang (王伟仙)
    • 1
  • Bao-ju Wang (王宝菊)
    • 1
  • Dong-liang Yang (杨东亮)
    • 1
  • Ping Wei (魏 屏)
    • 1
    Email author
  • Yin-ping Lu (卢银平)
    • 1
    Email author
  1. 1.Institute of Infection and Immunology, Department of Infectious Diseases, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

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