BACKGROUND/AIMS: Fibrotic liver remodelling was studied in culture of precision-cut liver slices (PCLS) derived from fibrotic liver. METHODS: Fibrosis was induced in rats by carbon tetrachloride (CCl4) treatment or bile duct ligation. Human fibrotic livers were also used. PCLS were cultured for 6, 24, 48, or 72 h, and the expression of alpha-smooth muscle (SM) actin, platelet-derived growth factor (PDGF) receptor-beta, and active caspase 3 was studied by immunohistochemistry. RESULTS: Before culture, in CCl4-treated or bile duct ligated animals, fibrosis was observed around centrolobular veins, or in portal zones, respectively. In PCLS derived from CCl4-treated animals, alpha-SM actin expression disappeared after 24h in culture while PDGF receptor-beta expression decreased progressively after 48 h. These changes were observed in absence of massive apoptosis. In PCLS derived from bile duct ligated animals, both alpha-SM actin and PDGF receptor-beta expression decreased after 48 h in culture with a massive apoptosis. In PCLS derived from human fibrotic livers, alpha-SM actin expression was dramatically reduced after 48 h in culture. CONCLUSIONS: After CCl4 treatment, a proportion of myofibroblasts derived from hepatic stellate cells seems to dedifferentiate while in bile duct ligation model, myofibroblasts derived from portal fibroblasts disappear by apoptosis, underlining the relevance of this model to evaluate the mechanisms involved in fibrotic liver remodelling.
BACKGROUND/AIMS: Fibrotic liver remodelling was studied in culture of precision-cut liver slices (PCLS) derived from fibrotic liver. METHODS:Fibrosis was induced in rats by carbon tetrachloride (CCl4) treatment or bile duct ligation. Human fibrotic livers were also used. PCLS were cultured for 6, 24, 48, or 72 h, and the expression of alpha-smooth muscle (SM) actin, platelet-derived growth factor (PDGF) receptor-beta, and active caspase 3 was studied by immunohistochemistry. RESULTS: Before culture, in CCl4-treated or bile duct ligated animals, fibrosis was observed around centrolobular veins, or in portal zones, respectively. In PCLS derived from CCl4-treated animals, alpha-SM actin expression disappeared after 24h in culture while PDGF receptor-beta expression decreased progressively after 48 h. These changes were observed in absence of massive apoptosis. In PCLS derived from bile duct ligated animals, both alpha-SM actin and PDGF receptor-beta expression decreased after 48 h in culture with a massive apoptosis. In PCLS derived from human fibrotic livers, alpha-SM actin expression was dramatically reduced after 48 h in culture. CONCLUSIONS: After CCl4 treatment, a proportion of myofibroblasts derived from hepatic stellate cells seems to dedifferentiate while in bile duct ligation model, myofibroblasts derived from portal fibroblasts disappear by apoptosis, underlining the relevance of this model to evaluate the mechanisms involved in fibrotic liver remodelling.
Authors: Boris Hinz; Sem H Phan; Victor J Thannickal; Marco Prunotto; Alexis Desmoulière; John Varga; Olivier De Wever; Marc Mareel; Giulio Gabbiani Journal: Am J Pathol Date: 2012-03-02 Impact factor: 4.307
Authors: Hiroshi Yagi; Edgar Tafaleng; Masaki Nagaya; Marc C Hansel; Stephen C Strom; Ira J Fox; Alejandro Soto-Gutierrez Journal: Crit Rev Biomed Eng Date: 2009
Authors: Inge A M de Graaf; Peter Olinga; Marina H de Jager; Marjolijn T Merema; Ruben de Kanter; Esther G van de Kerkhof; Geny M M Groothuis Journal: Nat Protoc Date: 2010-08-19 Impact factor: 13.491
Authors: Michael J Duryee; Benjamin M Wiese; Jordan R Bowman; Jared D Vanlandingham; Lynell W Klassen; Geoffrey E Thiele; Carlos D Hunter; Daniel R Anderson; Ted R Mikuls; Geoffrey M Thiele Journal: Am J Physiol Gastrointest Liver Physiol Date: 2017-12-28 Impact factor: 4.052
Authors: Ajit Dash; Walker Inman; Keith Hoffmaster; Samantha Sevidal; Joan Kelly; R Scott Obach; Linda G Griffith; Steven R Tannenbaum Journal: Expert Opin Drug Metab Toxicol Date: 2009-10 Impact factor: 4.481
Authors: Lynell W Klassen; Geoffrey M Thiele; Michael J Duryee; Courtney S Schaffert; Amy L DeVeney; Carlos D Hunter; Peter Olinga; Dean J Tuma Journal: Biochem Pharmacol Date: 2008-05-21 Impact factor: 5.858