Project Details
Projekt
Functional impact of ductular reaction on disease progression in pediatric cholangiopathies
Subject Area
Pediatric and Adolescent Medicine
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 556479455
Liver diseases comprise a broad range of genetic-, infection-, metabolism- and intoxication-related etiologies. Common feature in virtually all chronic liver diseases is the progressive loss of hepatocyte function combined with an alteration of the biliary epithelial cell architecture and microenvironment, i.e. ductular reaction. These unifying aspects of chronic liver diseases are currently not considered as co-dependent events and, accordingly, ductular reaction is regarded as an epiphenomenon. Ductular reaction is defined as the proliferation of immature, ductular cells, together with immune cell recruitment and local fibrogenesis. According to recent reports, ductular cells may result from trans-differentiation of injured cholangiocytes or transitioning hepatocytes. As such, ductular reaction may be seen as an overarching cellular response in chronic liver diseases, which is independent of hepatic progenitor cells. Yet, the disease-specific peculiarities of ductular reaction are still to be explored. We hypothesize that the origin of ductular cells differs between disease entities and determines disease progression, e.g., loss of hepatocyte functions, inflammation and fibrogenesis. Here, we aim at dissecting the functional characteristics of ductular reaction in prototypic pediatric liver diseases with distinct histological specificities, namely biliary atresia, Alagille syndrome, cystic fibrosis and primary sclerosing cholangitis. This project thus will contribute to identify novel therapeutic targets for chronic liver disease management, by defining ductular cell-driven mechanisms involved in physiological versus pathological liver response to cholestasis.
DFG Programme
Research Grants
