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 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.
Isono
Masato
M
Division of Molecular Biology, Department of Molecular and Cellular Biology, School of Life Science, Tottori University Faculty of Medicine, 683-8503, Yonago, Japan.
Soda
Mariko
M
Inoue
Asuka
A
Akiyoshi
Hideo
H
Sato
Kenzo
K
D000818:Animals; D002251:Carbon Tetrachloride; D002454:Cell Differentiation; D002460:Cell Line; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D010446:Peptide Fragments; D011498:Protein Precursors; D011994:Recombinant Proteins; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D002251:Carbon Tetrachloride