Characterization of liver disease regression in murine models of liver fibrosis and portal hypertension

作者：Philipp Königshofer, Ksenia Brusilovskaya, Benedikt Hofer, Oleksandr Petrenko, Benedikt Simbrunner, Katharina Bareiner, Kerstin Zinober, Katharina Regnat, Vlad Țâru, Thomas Sorz, Katharina Bonitz, Hubert Scharnagl, Tatjana Stojaković, Michael Trauner, Stefan G. Kauschke, Larissa Pfisterer, Philipp Schwabl, Thomas Reiberger · 发表于：Scientific Reports · 年份：2026 · DOI：10.1038/s41598-026-54627-5 · 研究领域：Liver physiology and pathology、Liver Disease Diagnosis and Treatment、Liver Disease and Transplantation

Characterization of toxin-induced mouse models of regressive liver disease, focusing on the detecting of a suitable therapeutic window during fibrosis and portal hypertension (PH) regression. C57BL/6JRj mice were studied when exposed to thioacetamide (TAA) or carbon tetrachloride (CCl 4 ) for 8 or 12 weeks (8w/12w) and after one/two (+R1/+R2) week(s) of TAA/CCl 4 -free regression. Healthy controls received NaCl or olive oil (OO). Primary readouts included liver fibrosis (collagen proportionate area, CPA), portal pressure (PP), serum transaminases and hepatic fibrosis-related gene expression. The diseased models (8wTAA/12wTAA/8wCCl 4 /12wCCl 4 ) showed significant fibrosis (CPA: 3.03/3.87/8.53/16.90%; vs. NaCl/OO: 0.87/1.15%) and PH (PP: 6.8/7.7/8.5/10.0 mmHg; vs. NaCl/OO: 5.5/5.1 mmHg). CPA significantly regressed in 8wTAA+R1 (2.60%; p = 0.01) and 12wCCl 4 +R1 (10.9%; p = 0.01), but not in 12wTAA+R1/8wCCl 4 +R1. CPA regression was significant in all +R2-groups ( p < 0.001) but not in 8wCCl 4 +R2 ( p = 0.30). Significant PP regression was found at 8wCCl 4 +R1 (5.8 mmHg; p = 0.004) and 12wCCl 4 +R1 (8.4 mmHg; p = 0.01), but not in the 8w/12w TAA models. All +R2-groups showed significant PP regression: 8wTAA+R2 (6.0 mmHg; p ≤ 0.001), 12wTAA+R2 (6.0 mmHg), 8wCCl 4 +R2 (6.0 mmHg, p = 0.004) and 12wCCl 4 +R2 (7.9 mmHg, p = 0.008). Serum AST/ALT levels at +R1/+R2 returned to levels of healthy controls. Hepatic Col1a1 and Timp1 gene expression peaked in 12w-groups and showed a gradua...