Reverse transformation of hepatic myofibroblast-like cells by TGFβ1/LAP

• Published in: Biochemical and biophysical research communications 2003-11, Vol.311 (4), p.959-965
• Main Authors: Isono, Masato, Soda, Mariko, Inoue, Asuka, Akiyoshi, Hideo, Sato, Kenzo
• Format: Article
• Language: English
• Subjects: Adenovirus vector; Extracellular matrix; Fibrogenesis; Hepatic stellate cell; Latency-associated peptide; Myofibroblast; Reverse transformation; TGFβ1
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2003.10.093

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 β1 (TGFβ1) 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 TGFβ1 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 TGFβ1 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 α-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.