{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:02:07Z","timestamp":1790650927437,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,10,23]],"date-time":"2017-10-23T00:00:00Z","timestamp":1508716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB\/TRR 57 P26\/P13"],"award-info":[{"award-number":["SFB\/TRR 57 P26\/P13"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2018,5]]},"abstract":"Abstract<\/jats:title>\n \n Background & Aims<\/jats:title>\n \n Liver fibrosis is the outcome of chronic liver injury. Transforming growth factor\u2010\u03b2 (\n TGF<\/jats:styled-content>\n \u2010\u03b2) is a major profibrogenic cytokine modulating hepatic stellate cell (\n HSC<\/jats:styled-content>\n ) activation and extracellular matrix homeostasis. This study analyses the effect of Endoglin (Eng), a\n TGF<\/jats:styled-content>\n \u2010\u03b2 type\n III<\/jats:styled-content>\n auxiliary receptor, on fibrogenesis in two models of liver injury by\n HSC<\/jats:styled-content>\n \u2010specific endoglin deletion.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Eng expression was measured in human and murine samples of liver injury. After generating GFAP\n Cre(+)<\/jats:sup>\n Eng\n \u0394<\/jats:sup>\n \n HSC<\/jats:sup>\n <\/jats:styled-content>\n mice, the impact of Endoglin deletion on chronic liver fibrosis was analysed. For in vitro analysis, Eng\n flox\/flox<\/jats:sup>\n HSC<\/jats:styled-content>\n s were infected with Cre\u2010expressing virus to deplete Endoglin and fibrogenic responses were analysed.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Endoglin is upregulated in human liver injury. The receptor is expressed in liver tissues and mesenchymal liver cells with much higher abundance of the L\u2010Eng splice variant. Comparing\n \n GFAP\n C<\/jats:sup>\n <\/jats:styled-content>\n re(\u2212)<\/jats:sup>\n Eng\n f\/f<\/jats:sup>\n to\n \n GFAP\n C<\/jats:sup>\n <\/jats:styled-content>\n re(+)<\/jats:sup>\n Eng\n \u0394<\/jats:sup>\n \n HSC<\/jats:sup>\n <\/jats:styled-content>\n mice in toxic liver injury, livers of\n \n GFAP\n C<\/jats:sup>\n <\/jats:styled-content>\n re(+)<\/jats:sup>\n Eng\n \u0394<\/jats:sup>\n \n HSC<\/jats:sup>\n <\/jats:styled-content>\n mice showed 39.9% (\n P<\/jats:italic>\n \u00a0<\u00a0.01) higher Hydroxyproline content compared to\n \n GFAP\n C<\/jats:sup>\n <\/jats:styled-content>\n re(\u2212)<\/jats:sup>\n Eng\n f\/f<\/jats:sup>\n littermates. Sirius Red staining underlined these findings, showing 58.8% (\n P<\/jats:italic>\n \u00a0<\u00a0.05) more Collagen deposition in livers of\n \n GFAP\n C<\/jats:sup>\n <\/jats:styled-content>\n re(+)<\/jats:sup>\n Eng\n \u0394<\/jats:sup>\n \n HSC<\/jats:sup>\n <\/jats:styled-content>\n mice. Similar results were obtained in mice subjected to cholestatic injury.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Endoglin isoforms are differentially upregulated in liver samples of patients with chronic and acute liver injury. Endoglin deficiency in\n HSC<\/jats:styled-content>\n significantly aggravates fibrosis in response to injury in two different murine models of liver fibrosis and increases \u03b1\u2010\n SMA<\/jats:styled-content>\n and fibronectin expression in vitro. This suggests that Endoglin protects against fibrotic injury, likely through modulation of\n TGF<\/jats:styled-content>\n \u2010\u03b2 signalling.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/liv.13595","type":"journal-article","created":{"date-parts":[[2017,9,20]],"date-time":"2017-09-20T11:46:44Z","timestamp":1505908004000},"page":"858-867","source":"Crossref","is-referenced-by-count":27,"title":["Endoglin in human liver disease and murine models of liver fibrosis\u2014A protective factor against liver fibrosis"],"prefix":"10.1111","volume":"38","author":[{"given":"Muhammad","family":"Alsamman","sequence":"first","affiliation":[{"name":"Department of Internal Medicine III RWTH University Hospital Aachen Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Sterzer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III RWTH University Hospital Aachen Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen K.","family":"Meurer","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry RWTH University Hospital Aachen Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hacer","family":"Sahin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III RWTH University Hospital Aachen Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Schaeper","sequence":"additional","affiliation":[{"name":"Silence Therapeutics GmbH Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deniz","family":"Kuscuoglu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III RWTH University Hospital Aachen Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Strnad","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III RWTH University Hospital Aachen Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3888-0931","authenticated-orcid":false,"given":"Ralf","family":"Weiskirchen","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry RWTH University Hospital Aachen Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Trautwein","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III RWTH University Hospital Aachen Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6531-513X","authenticated-orcid":false,"given":"David","family":"Scholten","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III RWTH University Hospital Aachen Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,10,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","unstructured":"SterzerV AlsammanM BretagT ScholtenD.EMT in Liver Fibrosis. 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