Reverse transformation of hepatic myofibroblast-like cells by TGFbeta1/LAP

The activation of hepatic stellate cells (HSCs) to myofibroblasts (MFBs) is a key process for initiation of hepatic fibrosis and accumulation of the extracellular matrix (ECM). In this process, transforming growth factor beta1 (TGFbeta1) plays an important role in activating HSCs. In this study, we...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2003-11, Vol.311 (4), p.959
Main Authors: Isono, Masato, Soda, Mariko, Inoue, Asuka, Akiyoshi, Hideo, Sato, Kenzo
Format: Article
Language:English
Subjects:
Animals
Carbon Tetrachloride
Cell Differentiation
Cell Line
Extracellular Matrix - metabolism
Fibroblasts - metabolism
Fibroblasts - pathology
Liver - metabolism
Liver - pathology
Liver Cirrhosis - chemically induced
Liver Cirrhosis - metabolism
Liver Cirrhosis - pathology
Male
Peptide Fragments - genetics
Peptide Fragments - metabolism
Protein Precursors - genetics
Protein Precursors - metabolism
Rats
Rats, Wistar
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Transforming Growth Factor beta - metabolism
Transforming Growth Factor beta1
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Summary:The activation of hepatic stellate cells (HSCs) to myofibroblasts (MFBs) is a key process for initiation of hepatic fibrosis and accumulation of the extracellular matrix (ECM). In this process, transforming growth factor beta1 (TGFbeta1) plays an important role in activating HSCs. In this study, we determined whether the activation of HSC was suppressed by latency-associated peptide (LAP) that is a part of TGFbeta1 precursor peptide. An MFB-like cell line (MFBY2) established from a fibrotic rat liver was infected with a recombinant adenovirus expressing LAP (AxCALAP). As results, AxCALAP-infected MFBY2 arrested cell proliferation and significantly decreased in expression of TGFbeta1 and ECM components. Interestingly, the expression of glial fibrillary acidic protein and up-take of retinoic acid were enhanced by AxCALAP-infection, while expression of alpha-smooth muscle actin was inhibited. These results suggested that overexpression of LAP in MFBs induces the reverse transformation to HSC phenotype. The adenoviral vector used in this study may have possible therapeutic applications in liver fibrosis.
ISSN:0006-291X