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Using a liver cancer dataset from the International Cancer Genome Consortium, we developed an extensive in silico screening that identified a cluster of adamalysins co\u2010expressed in livers from patients with hepatocellular carcinoma (HCC). Within this cluster,\n                    <jats:italic>ADAMTS12<\/jats:italic>\n                    expression was highly associated with recurrence risk and poorly differentiated HCC signatures. We showed that\n                    <jats:italic>ADAMTS12<\/jats:italic>\n                    was expressed in the stromal cells of the tumor and adjacent fibrotic tissues of HCC patients, and more specifically in activated stellate cells. Using a mouse model of carbon tetrachloride\u2010induced liver injury, we showed that A\n                    <jats:italic>damts12<\/jats:italic>\n                    was strongly and transiently expressed after a 24\u2009h acute treatment, and that fibrosis was exacerbated in\n                    <jats:italic>Adamts12<\/jats:italic>\n                    \u2010null mice submitted to carbon tetrachloride\u2010induced chronic liver injury. Using the HSC\u2010derived LX\u20102 cell line, we showed that silencing of\n                    <jats:italic>ADAMTS12<\/jats:italic>\n                    resulted in profound changes of the gene expression program. In particular, genes previously reported to be induced upon HSC activation, such as PAI\u20101, were mostly down\u2010regulated following\n                    <jats:italic>ADAMTS12<\/jats:italic>\n                    knock\u2010down. The phenotype of these cells was changed to a less differentiated state, showing an altered actin network and decreased nuclear spreading. These phenotypic changes, together with the down\u2010regulation of PAI\u20101, were offset by TGF\u2010\u03b2 treatment. The present study thus identifies ADAMTS12 as a modulator of HSC differentiation, and a new player in chronic liver disease.\n                  <\/jats:p>","DOI":"10.1096\/fj.202200692rrrr","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T01:50:03Z","timestamp":1697075403000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["<scp>ADAMTS12<\/scp>\n                    is a stromal modulator in chronic liver disease"],"prefix":"10.1096","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4235-7505","authenticated-orcid":false,"given":"Bassil","family":"Dekky","sequence":"first","affiliation":[{"name":"University of Rennes, INSERM, EHESP, IRSET (Institut de Recherche en Sant\u00e9, Environnement et Travail)\u2014UMR_S 1085  Rennes 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