{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T15:53:08Z","timestamp":1790610788230,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2014,8,25]],"date-time":"2014-08-25T00:00:00Z","timestamp":1408924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007197","name":"U.S. Public Health Service","doi-asserted-by":"publisher","award":["DK062092"],"award-info":[{"award-number":["DK062092"]}],"id":[{"id":"10.13039\/100007197","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01BX001746"],"award-info":[{"award-number":["I01BX001746"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006939","name":"Emory University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006939","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:p>\n                    Previous evidence indicates that adiponectin possesses antifibrogenic activity in inhibiting liver fibrosis. Therapeutic strategies, however, are limited by adiponectin quaternary structure and effective concentrations in circulation. Here we postulate a novel molecular mechanism, whereby adiponectin targets focal adhesion kinase (FAK) activity and disrupts key features of the fibrogenic response. Adiponectin\u2010null (Ad\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    ) mice and wild\u2010type littermates were exposed to either saline or carbon tetrachloride (CCl\n                    <jats:sub>4<\/jats:sub>\n                    ) for 6 wk. CCl\n                    <jats:sub>4<\/jats:sub>\n                    \u2010gavaged mice were also injected with attenuated adenoviral adiponectin (Ad\u2010Adn) or Ad\u2010LacZ for 2 wk. Hepatic stellate cells (HSCs) were treated with or without adiponectin to elucidate signal transduction mechanisms.\n                    <jats:italic>In vivo<\/jats:italic>\n                    delivery of Ad\u2010Adn markedly attenuates CCl\n                    <jats:sub>4<\/jats:sub>\n                    \u2010induced expression of key integrin proteins and markers of HSC activation: \u03b1v, \u03b23, \u03b21, \u03b12(I) collagen, and \u03b1\u2010smooth muscle actin. Confocal experiments of liver tissues demonstrated that adiponectin delivery also suppressed vinculin and p\u2010FAK activity in activated HSCs.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , adiponectin induced dephosphorylation of FAK, mediated by a physical association with activated tyrosine phosphatase, Shp2. Conversely, Shp2 knockdown by siRNA significantly attenuated adiponectin\u2010induced FAK deactivation, and expression of TIMP1 and \u03b12(I) collagen was abolished in the presence of adiponectin and si\u2010FAK. Finally, we documented that either adiponectin or the synthetic peptide with adiponectin properties, ADP355, suppressed p\u2010FAK in synthetic matrices with stiffness measurements of 9 and 15 kPa, assessed by immunofluorescent imaging and quantitation. The\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    data presented indicate that disassembly of focal adhesion complexes in HSCs is pivotal for hepatic fibrosis therapy, now that small adiponectin\u2010like peptides are available.\u2014Kumar, P., Smith, T., Rahman, K., Mells, J. E., Thorn, N. E., Saxena, N. K., Anania, F. A., Adiponectin modulates focal adhesion disassembly in activated hepatic stellate cells: implication for reversing hepatic fibrosis. FASEB J. 28, 5172\u20135183 (2014).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.14-253229","type":"journal-article","created":{"date-parts":[[2014,8,25]],"date-time":"2014-08-25T22:44:00Z","timestamp":1409006640000},"page":"5172-5183","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Adiponectin modulates focal adhesion disassembly in activated hepatic stellate cells: implication for reversing hepatic fibrosis"],"prefix":"10.1096","volume":"28","author":[{"given":"Pradeep","family":"Kumar","sequence":"first","affiliation":[{"name":"Division of Digestive Diseases Department of Medicine Emory University School of Medicine Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tekla","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Digestive Diseases Department of Medicine Emory University School of Medicine Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalidur","family":"Rahman","sequence":"additional","affiliation":[{"name":"Division of Digestive Diseases Department of Medicine Emory University School of Medicine Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie E.","family":"Mells","sequence":"additional","affiliation":[{"name":"Division of Digestive Diseases Department of Medicine Emory University School of Medicine Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie E.","family":"Thorn","sequence":"additional","affiliation":[{"name":"Division of Digestive Diseases Department of Medicine Emory University School of Medicine Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeraj K.","family":"Saxena","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology University of Maryland School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank A.","family":"Anania","sequence":"additional","affiliation":[{"name":"Division of Digestive Diseases Department of Medicine Emory University School of Medicine Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,8,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20060242"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.04.011"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20425"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-1847fje"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-006-9244-8"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-2760(01)00524-0"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-13-0578"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-0806"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2013.03.003"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20102148"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpgasthep0055"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23754"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2010.97"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3282"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2007.08.010"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2007.00901.x"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00412.2010"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6750-11-90"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-008-0544-2"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2011.10.011"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M513040200"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11684-012-0216-4"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-230X(10)06002-1"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI43464"},{"key":"e_1_2_7_26_1","first-page":"725","article-title":"Crosstalk between high\u2010molecular\u2010weight adiponectin and T\u2010cadherin during liver fibrosis development in rats","volume":"20","author":"Asada K.","year":"2007","journal-title":"Int. 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