Impact of pharmacological sGC stimulation with Riociguat in experimental models of liver disease regression

作者：Katharina Bonitz, Philipp Königshofer, Henriette Horstmeier, Thomas Sorz, Vlad Țâru, Katharina Bareiner, Oleksander Petrenko, Benedikt Simbrunner, Benedikt Hofer, Georg KRAMER, Katja Sommer, Kerstin Zinober, Katharina Regnat, Hubert Scharnagl, Peng Yan Sun, Eric Simon, Stefan Kauscke, Michael Trauner, Thomas Reiberger, Philipp Schwabl · 发表于：Hepatology International · 年份：2026 · DOI：10.1007/s12072-026-11086-4 · 研究领域：Liver physiology and pathology、Nitric Oxide and Endothelin Effects、Sulfur Compounds in Biology

Abstract Background Liver fibrosis and portal hypertension (PH) determine prognosis in chronic liver disease. In experimental models, stimulation of NO–sGC–cGMP signaling improved fibrosis, PH and inflammation. Since fibrosis and PH improve slowly after injury cessation, we investigated whether stimulating sGC activity accelerates their regression. Methods Liver fibrosis was induced in C57BL/6 J mice by either carbon tetrachloride (CCl 4 ; 2 µl/g, gavage 3x/week) for 12 weeks or thioacetamide (TAA; 150 mg/kg, intraperitoneal injections 3x/week) for 12 weeks, followed by 1 (R1) or 2 (R2) weeks of regression. Animals received the sGC stimulator Riociguat (RIO; 3 mg/kg, gavage 2x/day) during regression. Disease severity was assessed by portal pressure (PP), collagen proportionate area (CPA) and whole liver transcriptomics. Results PH and fibrosis area peaked in the TAA model at 7.71 ± 0.57 mmHg PP and 3.87 ± 0.19% CPA; and in the CCl 4 model at 9.06 ± 0.89 mmHg PP and 9.43 ± 2.59% CPA, respectively; followed by spontaneous regression at R2 (TAA: PP: 6.04 ± 0.52 mmHg, CPA: 2.90 ± 0.30%; CCl 4 : PP: 5.88 ± 0.52 mmHg, CPA: 6.66 ± 1.45%). RIO significantly increased hepatic cGMP levels (CCl 4 –R2: 5.89 ± 0.58 nmol/L, R2 + RIO: 12.41 ± 1.98 nmol/L). While fibrosis and PH regression were not significantly different, RIO treatment attenuated the hepatic pro-inflammatory gene signatures in both models and improved metabolic pathways on a transcriptional level. Conclusions Riociguat incr...