{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:10:26Z","timestamp":1790971826235,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,1,30]],"date-time":"2022-01-30T00:00:00Z","timestamp":1643500800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p><jats:italic>PTTG1<\/jats:italic> is almost undetectable in adult livers but is highly expressed in hepatocarcinoma. While little is known about its involvement in liver fibrosis, <jats:italic>PTTG1<\/jats:italic> expression is associated with <jats:italic>DLK1<\/jats:italic>. We assessed the role of the <jats:italic>PTTG1\/DLK1<\/jats:italic> pathway in fibrosis progression and the potential therapeutic effect of <jats:italic>PTTG1<\/jats:italic> silencing in fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:italic>Pttg1<\/jats:italic> and <jats:italic>Dlk1<\/jats:italic> were studied in liver and isolated cell populations of control and fibrotic rats and in human liver biopsies. The fibrotic molecular signature was analysed in <jats:italic>Pttg1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> and <jats:italic>Pttg1<\/jats:italic><jats:sup><jats:italic>+\/+<\/jats:italic><\/jats:sup> fibrotic mice. Finally, <jats:italic>Pttg1<\/jats:italic> silencing was evaluated in rats as a novel antifibrotic therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>Pttg1<\/jats:italic> and <jats:italic>Dlk1<\/jats:italic> mRNA selectively increased in fibrotic rats paralleling fibrosis progression. Serum DLK1 concentrations correlated with hepatic collagen content and systemic and portal haemodynamics. Human cirrhotic livers showed greater <jats:italic>PTTG1<\/jats:italic> and <jats:italic>DLK1<\/jats:italic> transcript abundance than non\u2010cirrhotic, and reduced collagen was observed in <jats:italic>Pttg1<\/jats:italic> <jats:italic>Pttg1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice. The liver fibrotic molecular signature revealed lower expression of genes related to extracellular matrix remodelling including <jats:italic>Mmp<\/jats:italic>8 and <jats:italic>9<\/jats:italic> and <jats:italic>Timp4<\/jats:italic> and greater <jats:italic>eotaxin<\/jats:italic> and <jats:italic>Mmp13<\/jats:italic> than fibrotic <jats:italic>Pttg1<\/jats:italic><jats:sup><jats:italic>+\/+<\/jats:italic><\/jats:sup> mice. Finally, interfering <jats:italic>Pttg1<\/jats:italic> resulted in reduced liver fibrotic area, lower <jats:italic>\u03b1\u2010Sma<\/jats:italic> and decreased portal pressure than fibrotic animals. Furthermore, <jats:italic>Pttg1<\/jats:italic> silencing decreased the transcription of <jats:italic>Dlk1<\/jats:italic>, <jats:italic>collagens I<\/jats:italic> and <jats:italic>III<\/jats:italic>, <jats:italic>Pdgfr\u03b2<\/jats:italic>, <jats:italic>Tgfr\u03b2<\/jats:italic>, <jats:italic>Timp1<\/jats:italic>, <jats:italic>Timp2<\/jats:italic> and <jats:italic>Mmp2<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:italic>Pttg1<\/jats:italic>\/<jats:italic>Dlk1<\/jats:italic> are selectively overexpressed in the cirrhotic liver and participate in ECM turnover regulation. <jats:italic>Pttg1<\/jats:italic> disruption decreases <jats:italic>Dlk1<\/jats:italic> transcription and attenuates collagen deposition. <jats:italic>PTTG1\/DLK1<\/jats:italic> signalling is a novel pathway for targeting the progression of liver fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15165","type":"journal-article","created":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T16:45:11Z","timestamp":1642697111000},"page":"651-662","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The pituitary tumour\u2010transforming gene 1\/delta\u2010like homologue 1 pathway plays a key role in liver fibrogenesis"],"prefix":"10.1111","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1944-8337","authenticated-orcid":false,"given":"Meritxell","family":"Perram\u00f3n","sequence":"first","affiliation":[{"name":"Biochemistry and Molecular Genetics Service Hospital Cl\u00ednic Universitari Barcelona Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEReHD) Barcelona 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