Stellate cell apoptosis by a soluble mediator from immortalized human hepatocytes |
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Authors: | Arnab Basu Kousuke Saito Keith Meyer Ratna B Ray Scott L Friedman Yie-Hwa Chang Ranjit Ray |
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Institution: | (1) Department of Internal Medicine, Saint Louis University, St. Louis, MO, 63110;(2) Department of Pathology, Saint Louis University, St. Louis, MO, 63110;(3) Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY, 10029;(4) Department of Biochemistry & Molecular Biology, Saint Louis University, St. Louis, MO, 63110;(5) Division of Infectious Diseases and Immunology, Department of Molecular Microbiology & Immunology, Saint Louis University, 3635 Vista Avenue, FDT-8N, St. Louis, MO, 63110 |
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Abstract: | Activated hepatic stellate cells (HSCs) are the major source of extracellular matrix in fibrosis and cirrhosis. In this study,
we have investigated the role of hepatitis C virus (HCV) core protein induced immortalized human hepatocytes (IHH) on HSC
growth. Preferential growth of IHH and apoptosis of activated human hepatic stellate cells (LX2) were observed upon coculture
of these two cell types in a dual chamber or in the presence of conditioned medium (CM) from IHH. CM did not display a growth
inhibitory role on other hepatic (Huh-7, HepG2, Hep3B and THLE) and non-hepatic (HeLa, MCF-7, and BHK) epithelial cells, indicating
that the soluble mediator from IHH does not have a generalized effect on cell lines examined in our study. Further studies
suggested that CM from IHH increased the expression of TRAIL receptors on LX2 cell surface, and induced apoptosis by a caspase
dependent mechanism. Peptide mass fingerprinting of the purified soluble mediator from CM suggested that gelsolin fragments
may play a role in apoptosis of LX2 cells. Taken together, our results suggested that a soluble mediator secreted from immortalized
human hepatocytes plays an important role in hepatic stellate cell growth regulation. |
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Keywords: | Apoptosis Gelsolin fragments Hepatocytes Peptide mass fingerprinting Stellate cells Soluble mediator |
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