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

Abstract

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 alpha-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.

DOI: 10.1111/j.1478-3231.2009.02120.x

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@article{Shimada2010GeneEP, title={Gene expression profiling and functional assays of activated hepatic stellate cells suggest that myocardin has a role in activation.}, author={Hideaki Shimada and Takashi Ochi and Akira Imasato and Yoshihito Morizane and Masatoshi Hori and Hiroshi Ozaki and Katsuhiro Shinjo}, journal={Liver international : official journal of the International Association for the Study of the Liver}, year={2010}, volume={30 1}, pages={42-54} }