Details

Autor(en) / Beteiligte

• Shimada, Hideaki
• Ochi, Takashi
• Imasato, Akira
• Morizane, Yoshihito
• Hori, Masatoshi
• Ozaki, Hiroshi
• Shinjo, Katsuhiro

Titel

Gene expression profiling and functional assays of activated hepatic stellate cells suggest that myocardin has a role in activation

Ist Teil von

• Liver international, 2010-01, Vol.30 (1), p.42-54

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• Background: Myofibroblast‐like cells derived from transdifferentiated hepatic stellate cells (HSC) play a central role in scar formation that leads to liver fibrosis. The molecular mechanisms underlying this process are not fully understood. Aim: Our aim was to identify genes that are differentially regulated by HSC activation and to explore their function. Methods: Using oligonucleotide microarrays, we performed transcriptional analysis of the human HSC cell line, LI90, cultured on Matrigel. Microarray data were validated by quantitative real‐time polymerase chain reaction and Western blotting. The function of myocardin was assessed by myocardin RNAi and overexpression. Results: Examination of Matrigel‐induced deactivation of LI90 cells revealed marked downregulation of myocardin, an important transcriptional regulator in smooth and cardiac muscle development. Small interfering RNA‐mediated suppression of myocardin expression in both activated LI90 and rat activated HSC resulted in loss of the phenotypic characteristics of myofibroblasts and significantly impaired the production of activated HSC markers, such as α‐smooth muscle actin and extracellular matrix proteins like type I collagen. Overexpression of myocardin led to the upregulation of these marker genes. Myocardin was upregulated in rat primary HSC during in vitro activation and in the fibrotic liver of a dimethylnitrosamine‐induced fibrosis rat model. Conclusions: This study demonstrates that myocardin is involved in the activation of HSC; myocardin may serve as a novel therapeutic target in the treatment of liver fibrosis.