{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T09:02:36Z","timestamp":1762160556554,"version":"3.30.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":3287,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,9]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>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 CCl4-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.<\/jats:bold>\n                                 <jats:bold>\n                                    In conclusion\n                                 <\/jats:bold>\n                                 <jats:bold>, ILK plays a key role in HSC activation and could be a possible target for antifibrogenic therapy.<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.21315","type":"journal-article","created":{"date-parts":[[2006,8,30]],"date-time":"2006-08-30T02:01:24Z","timestamp":1156903284000},"page":"612-622","update-policy":"http:\/\/dx.doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":45,"title":["Involvement of integrin-linked kinase in carbon tetrachloride\u2013induced hepatic fibrosis in rats"],"prefix":"10.1097","volume":"44","author":[{"given":"Yining","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadashi","family":"Ikegami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Honda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teruo","family":"Miyazaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard","family":"Bouscarel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcos","family":"Rojkind","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ichinosuke","family":"Hyodo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasushi","family":"Matsuzaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-12-20241201","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1074\/jbc.275.4.2247","article-title":"Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury.","volume":"275","author":"Friedman","year":"2000","journal-title":"J Biol Chem"},{"key":"R2-12-20241201","doi-asserted-by":"crossref","first-page":"d808","DOI":"10.2741\/reeves","article-title":"Activation of hepatic stellate cellsa key issue in liver fibrosis.","volume":"7","author":"Reeves","year":"2002","journal-title":"Front Biosci"},{"key":"R3-12-20241201","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1136\/gut.50.4.571","article-title":"Hepatic stellate cells: role in microcirculation and pathophysiology of portal hypertension.","volume":"50","author":"Reynaert","year":"2002","journal-title":"Gut"},{"key":"R4-12-20241201","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1055\/s-2001-17550","article-title":"History, heterogeneity, developmental biology, and functions of quiescent hepatic stellate cells.","volume":"21","author":"Geerts","year":"2001","journal-title":"Semin Liver Dis"},{"key":"R5-12-20241201","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1055\/s-2007-1007128","article-title":"Biology of hepatic stellate cells and their possible relevance in the pathogenesis of portal hypertension in cirrhosis.","volume":"19","author":"Pinzani","year":"1999","journal-title":"Semin Liver Dis"},{"key":"R6-12-20241201","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1034\/j.1600-0676.2002.01726.x","article-title":"Mesenchymal cells in the liverone cell type or two?","volume":"22","author":"Ramadori","year":"2002","journal-title":"Liver"},{"key":"R7-12-20241201","doi-asserted-by":"crossref","first-page":"G435","DOI":"10.1152\/ajpgi.00441.2001","article-title":"Rat liver myofibroblasts and hepatic stellate cells differ in CD95mediated apoptosis and response to TNFalpha.","volume":"283","author":"Saile","year":"2002","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"R8-12-20241201","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1172\/JCI1018","article-title":"Mechanisms of spontaneous resolution of rat liver fibrosis. 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