Dissecting the molecular antifibrotic effect of the TGF-Beta(I) receptor kinase inhibitor galunisertib in precision-cut liver slices

Exploring organ-specific features of fibrogenesis using murine precision-cut tissue slices

Fibrosis is the hallmark of pathologic tissue remodelling in most chronic diseases. Despite advances in our understanding of the mechanisms of fibrosis, it remains uncured. Fibrogenic processes share conserved core cellular and molecular pathways across organs. In this study, we aimed to elucidate shared and organ-specific features of fibrosis using murine precision-cut tissue slices (PCTS) prepared from small intestine, liver and kidneys. PCTS displayed substantial differences in their baseline gene expression profiles: 70% of the extracellular matrix (ECM)-related genes were differentially expressed across the organs. Culture for 48 h induced significant changes in ECM regulation and trig…

1st International Conference on Fatty Liver (ICFL). Seville, June 1-3, 2017: Abstracts

Evaluating the antifibrotic potency of galunisertib in a human ex vivo model of liver fibrosis

Background and Purpose Liver fibrosis is a major cause of liver-related mortality and, so far, no effective antifibrotic drug is available. Galunisertib, a TGF-β receptor type I kinase inhibitor, is a potential candidate for the treatment of liver fibrosis. Here, we evaluated the potency of galunisertib in a human ex vivo model of liver fibrosis. Experimental Approach Antifibrotic potency and associated mechanisms were studied ex vivo, using both healthy and cirrhotic human precision-cut liver slices. Fibrosis-related parameters, both transcriptional and translational level, were assessed after treatment with galunisertib. Key Results Galunisertib showed a prominent antifibrotic potency. Ph…