Figure 4
Riociguat reduces hepatic inflammation. RT-PCR was performed in liver tissue to screen for expression changes of inflammatory marker. (A) In the early BDL model expression differences were mostly non-significant, when compared to SO-VEH. Yet, in RIO treated animals mean VCAM and TNFα were decreased by 48.5% and 46.7%, respectively. (B) In advanced BDL animals, RIO significantly decreased TNFα and tended to reduce MCP1 expression. (C) Western Blotting was used to measure hepatic TNFα protein content, which significantly decreased in BDL rats receiving RIO. (D) Transaminases AST and ALT were measured in serum samples. RIO caused a significant decrease of AST and a trend towards lower ALT levels in rats with advanced BDL. (E) Hepatic immunohistochemistry stainings of CD68 positive cells were quantified to assess macrophage infiltration. In advanced BDL rats CD68 positive cell content was significantly decreased after RIO treatment. Full-length blots of the cropped lines [q, r] are presented in Supplementary Figure S5. *p < 0.05, **p < 0.01, ***p < 0.001 vs. BDL-VEH; two-sided unpaired t-test; n = 5–8 per group in panel A, B, D and E - according to Table 1; n = 3 per group in panel C.
