{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T07:18:43Z","timestamp":1785395923592,"version":"3.56.0"},"reference-count":34,"publisher":"Portland Press Ltd.","issue":"6","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,3,1]]},"abstract":"<jats:p>Inhibition or blockade of HSCs (hepatic stellate cells), the main matrix-producing cells involved in the wound-healing response, represents an attractive strategy for the treatment of liver fibrosis. In vitro studies have shown that activation of AMPK (AMP-activated protein kinase), a key player in the regulation of cellular energy homoeostasis, inhibits proliferation of myofibroblasts derived from HSCs. If AMPK is a true regulator of fibrogenesis then defective AMPK activity would enhance fibrogenesis and hepatic fibrosis. To test this, in the present work, in vitro studies were performed on mouse primary HSCs treated or not with the AMPK activator AICAR (5-amino-4-imidazolecarboxamide ribonucleotide) or isolated from mice lacking the AMPK\u03b11 catalytic subunit (AMPK\u03b11\u2212\/\u2212) or their littermates (AMPK\u03b11+\/+). Liver fibrosis was induced in vivo in AMPK\u03b11\u2212\/\u2212 and AMPK\u03b11+\/+ mice by repeated injections of CCl4 (carbon tetrachloride). During culture activation of HSCs, AMPK protein and activity significantly increased and regulatory AMPK\u03b33 mRNA was specifically up-regulated. Stimulation of AMPK activity by AICAR inhibited HSC proliferation, as expected, as well as collagen \u03b11(I) expression. Importantly, AMPK\u03b11 deletion inhibited proliferation of HSCs, but not fibrogenesis, in vivo. Moreover, AMPK\u03b11 deletion was not associated with enhanced CCl4-induced fibrosis in vivo. In conclusion, our present findings demonstrate that HSC transdifferentiation is associated with increased AMPK activity that could relate to the stabilization of AMPK complex by the \u03b33 subunits. Activation of AMPK in HSCs inhibits in vitro fibrogenesis. By contrast, low AMPK activity does not prevent HSC activation in vitro nor in in vivo fibrosis.<\/jats:p>","DOI":"10.1042\/cs20090293","type":"journal-article","created":{"date-parts":[[2009,11,2]],"date-time":"2009-11-02T15:31:43Z","timestamp":1257175903000},"page":"411-420","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Development of hepatic fibrosis occurs normally in AMPK-deficient mice"],"prefix":"10.1042","volume":"118","author":[{"given":"Alain","family":"Da\u00a0Silva\u00a0Morais","sequence":"first","affiliation":[{"name":"Gastroenterology Laboratory, Universit\u00e9 catholique de Louvain (UCL), B-1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Abarca-Quinones","sequence":"additional","affiliation":[{"name":"Gastroenterology Laboratory, Universit\u00e9 catholique de Louvain (UCL), B-1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Guigas","sequence":"additional","affiliation":[{"name":"Hormone and Metabolic Research Unit, Universit\u00e9 catholique de Louvain (UCL) and de Duve Institute, B-1200 Brussels, Belgium"},{"name":"Department of Molecular Cell Biology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Viollet","sequence":"additional","affiliation":[{"name":"Institut Cochin, Universit\u00e9 Paris Descartes, CNRS UMR 8104, Department of Endocrinology, Metabolism and Cancer, Paris 75014, France"},{"name":"INSERM U567, Paris 75014, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"St\u00e4rkel","sequence":"additional","affiliation":[{"name":"Gastroenterology Laboratory, Universit\u00e9 catholique de Louvain (UCL), B-1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Horsmans","sequence":"additional","affiliation":[{"name":"Gastroenterology Laboratory, Universit\u00e9 catholique de Louvain (UCL), B-1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle\u00a0A.","family":"Leclercq","sequence":"additional","affiliation":[{"name":"Gastroenterology Laboratory, Universit\u00e9 catholique de Louvain (UCL), B-1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2009,12,14]]},"reference":[{"key":"2021113010170141000_B1","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1053\/j.gastro.2003.08.029","article-title":"Enhanced carbon tetrachloride-induced liver fibrosis in mice lacking adiponectin","volume":"125","author":"Kamada","year":"2003","journal-title":"Gastroenterology"},{"key":"2021113010170141000_B2","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1016\/S0002-9440(10)62476-5","article-title":"The roles of leptin and adiponectin: a novel paradigm in adipocytokine regulation of liver fibrosis and stellate cell biology","volume":"166","author":"Ding","year":"2005","journal-title":"Am. 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