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Recombinant human Hepassocin stimulates proliferation of hepatocytes in vivo and Improves Survival in Rats with Fulminant Hepatic Failure
  1. Chang-Yan Li1,
  2. Chuan-Zeng Cao1,
  3. Wang-Xiang Xu1,
  4. Meng-Meng Cao1,
  5. Fan Yang1,
  6. Lan Dong2,
  7. Miao Yu1,
  8. Yi-Qun Zhan1,
  9. Ya-Bin Gao1,
  10. Wei Li1,
  11. Zhi-Dong Wang1,
  12. Chang-Hui Ge1,
  13. Qing-Ming Wang1,
  14. Rui-Yun Peng1,
  15. Xiao-Ming Yang1,*
  1. 1 Beijing Institute of Radiation Medicine, China;
  2. 2 General Hospital of Chinese People's Armed Police Forces, China
  1. Correspondence to: xiaoming Yang, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing, 100850, China; xiaomingyang{at}


Background: Human hepassocin (HPS) was originally detected by subtractive and differential cDNA cloning as a liver-specific gene that was markedly up-regulated during liver regeneration. Previous studies suggested that HPS showed mitogenic activity on isolated hepatocytes in vitro. However, its in vivo functions remained largely unknown. Therefore, we investigated the function of recombinant human HPS during liver regeneration and chemically induced liver injury.

Methods: The proliferation of primary hepatocytes was examined by [3H]Thymidine incorporation and immunohistological staining of PCNA. RNA interference (RNAi) was performed to knock-down the endogenous expression of HPS. The proliferation of L02 cells was examined by MTS assay. The phosphorylation of ERK1/2 was investigated by Western blotting analysis. Assessment of liver injury (histology, serum ALT and AST levels), apoptosis by TUNEL assay, were performed.

Results: Purified recombinant human HPS showed specific mitogenic activity on primary hepatocytes and normal liver cell lines in a MAPK-dependent manner and stimulated the proliferation of hepatocytes in rats with 70% PHx. Administration of HPS in rats after D-gal and CCl4 treatment protected against the liver injury (minimal liver necrosis, depressed ALT and AST levels, and decreased lethality), reduced apoptosis and enhanced proliferation. Knock-down of endogenous HPS in vivo enhanced the liver injury induced by D-gal by increasing the apoptosis and elevated ALT and AST levels.

Conclusions: HPS is a hepatic growth factor to accelerate hepatocytes proliferation in vivo and protect against liver injury. These data point out the potential interest of HPS in the treatment of FHF.

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