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 [(3)H]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 (CCl(4)) 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.
BACKGROUND:Humanhepassocin (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 humanHPS during liver regeneration and chemically induced liver injury was investigated. METHODS: The proliferation of primary hepatocytes was examined by [(3)H]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 humanHPS 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 (CCl(4)) 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.
Authors: Jun Wang; Miguel F Sanmamed; Ila Datar; Tina Tianjiao Su; Lan Ji; Jingwei Sun; Ling Chen; Yusheng Chen; Gefeng Zhu; Weiwei Yin; Linghua Zheng; Ting Zhou; Ti Badri; Sheng Yao; Shu Zhu; Agedi Boto; Mario Sznol; Ignacio Melero; Dario A A Vignali; Kurt Schalper; Lieping Chen Journal: Cell Date: 2018-12-20 Impact factor: 41.582
Authors: Y Zhang; D Dilimulati; D Chen; M Cai; H You; H Sun; X Gao; X Shao; M Zhang; S Qu Journal: J Endocrinol Invest Date: 2022-07-05 Impact factor: 5.467
Authors: Hamed Nayeb-Hashemi; Anal Desai; Valeriy Demchev; Roderick T Bronson; Jason L Hornick; David E Cohen; Chinweike Ukomadu Journal: Biochem Biophys Res Commun Date: 2015-07-28 Impact factor: 3.575