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Involvement of integrin‐linked kinase in carbon tetrachloride–induced hepatic fibrosis in rats
Author(s) -
Zhang Yining,
Ikegami Tadashi,
Honda Akira,
Miyazaki Teruo,
Bouscarel Bernard,
Rojkind Marcos,
Hyodo Ichinosuke,
Matsuzaki Yasushi
Publication year - 2006
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21315
Subject(s) - hepatic stellate cell , integrin linked kinase , hepatic fibrosis , fibrosis , cancer research , signal transduction , gsk3b , microbiology and biotechnology , downregulation and upregulation , focal adhesion , integrin , biology , chemistry , medicine , phosphorylation , endocrinology , protein kinase b , protein kinase a , receptor , biochemistry , cyclin dependent kinase 2 , gene
Integrin‐linked kinase (ILK) is a multidomain focal adhesion protein implicated in signal transduction between integrins and growth factor receptors. Although its expression is upregulated in pulmonary and renal fibrosis, its role in the development of hepatic fibrosis remains to be determined. Therefore, we considered it important to investigate whether ILK is involved in activation of hepatic stellate cells and thus plays a role in the development of hepatic fibrosis. Immunohistochemical analysis of liver sections obtained from rats with CCl 4 ‐induced cirrhosis revealed increased expression and colocalization of ILK and alpha‐smooth muscle actin in hepatic stellate cells in perisinusoidal areas. In addition, hepatic stellate cells isolated from fibrotic livers expressed high levels of ILK and alpha‐smooth muscle actin, and their expression was sustained in culture. In contrast, hepatic stellate cells (HSCs) isolated from normal rat liver did not express ILK, but its expression was increased when the cells were activated in culture. Our studies also showed that ILK is involved in the phosphorylation of ERK 1/2, p38 MAPK, JNK, and PKB and that selective inhibition of ILK expression by siRNA results in a significant decrease in their phosphorylation. These changes were accompanied by significant inhibition of cell spreading and migration without affecting cell proliferation. In conclusion , ILK plays a key role in HSC activation and could be a possible target for antifibrogenic therapy. (H EPATOLOGY 2006;44:612–622.)