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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 Xu2,
  4. Meng-Meng Cao3,
  5. Fan Yang4,
  6. Lan Dong5,
  7. Miao Yu1,
  8. Yi-Qun Zhan1,
  9. Ya-Bing Gao1,
  10. Wei Li1,
  11. Zhi-Dong Wang1,
  12. Chang-Hui Ge1,
  13. Qing-Ming Wang2,
  14. Rui-Yun Peng1,
  15. Xiao-Ming Yang2
  1. 1Beijing Institute of Radiation Medicine, Beijing, China
  2. 2State Key laboratory of Proteomics, Beijing, China
  3. 3Department of Pharmaceutical Engineering, Tianjin University, Tianjin China
  4. 4Department of Pathophysiology, Anhui Medical University, He Fei, China
  5. 5Department of Anesthesiology, General Hospital of Chinese People's Armed Police Forces, Beijing, China
  1. Correspondence to Dr Xiaoming Yang, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, PR China; xmyang2{at} or xiaomingyang{at}


Background Human hepassocin (HPS) was originally detected by subtractive and differential cDNA cloning as a liver-specific gene that was markedly upregulated 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, the function of recombinant human HPS during liver regeneration and chemically induced liver injury was investigated.

Methods The proliferation of primary hepatocytes was examined by [3H]thymidine incorporation and immunohistological staining of proliferating cell nuclear antigen (PCNA). RNA interference 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 (extracellular signal-regulated kinase 1/2) was investigated by western blotting analysis. Assessment of liver injury (histology, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels) and of apoptosis, by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay, was performed.

Results Purified recombinant human HPS showed specific mitogenic activity on primary hepatocytes and normal liver cell lines in a mitogen-activated protein kinase (MAPK)-dependent manner and stimulated the proliferation of hepatocytes in rats with 70% partial hepatectomy. Administration of HPS to rats after d-galactose and carbon tetrachloride (CCl4) treatment protected against 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-galactose by increasing the apoptosis and elevating ALT and AST levels.

Conclusions HPS is a hepatic growth factor which can accelerate hepatocyte proliferation in vivo and protect against liver injury. These data point to the potential interest of HPS in the treatment of fulminant hepatic failure.

  • FHF
  • hepatocyte proliferation
  • HPS
  • liver failure
  • liver regeneration

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  • Funding This work was partially supported by the Special Funds for Major State Basic Research of China (2006CB910802. 2009ZX09103-615), National HighTec Research Developing Program (2006AA02A310), Chinese National Natural Science Fund for the Popularisation of Science (30321063) and Chinese National Science Foundation Key Program Projects (30630035).

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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