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SFB 974:  Communication and System Relevance in Liver Injury and Regeneration

Subject Area Medicine
Biology
Term from 2012 to 2020
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 190586431
 
Due to their high prevalence, liver diseases are of great clinical and socio-economic importance. Liver diseases are frequently chronic and are systemically relevant because they can affect the function of other organ systems (e.g. kidney, brain, intestine, cardiovascular system, blood, endocrine system, immune system). Clinical presentation and prognosis of liver diseases are often determined by these extrahepatic manifestations. Conversely, other organ systems also influence liver function. Such system crosstalk does not only affect liver function or the extent and course of liver damage, but also the regenerative processes in the liver that are launched by the damaging events themselves. The remarkable ability of the liver to regenerate serves to safeguard vital liver functions and is observed not only after partial hepatectomy, but also in response to any kind of liver injury. The events that lead to the restoration of liver tissue at the molecular, cellular, organ and systemic level are complex and only incompletely understood. They comprise not only the proliferation of hepatocytes and, if necessary, the recruitment of stem/ progenitor cell compartments, but also a multitude of other factors that control the regeneration process. Since many of these factors are also involved in the pathogenesis of liver damage, it becomes clear that liver damage and regeneration are closely interrelated. A central hypothesis of the CRC 974 is that the sensitive balance between liver damage and regeneration is maintained through neuroendocrine, metabolic and immunological factors. Changes in this mediator pattern determine the outcome of liver damage and regeneration and may result in progressive injury or excessive regenerative processes and tumorigenesis. The factors affecting this balance include cytokines, chemokines, growth factors, cell hydration and organic osmolytes, extracellular matrix constituents, complement factors, bile salts and liver pathogens. Depending on the predominant factor the balance can be shifted either in favour of regeneration or in the direction of damage. Thus, regeneration can be influenced therapeutically in principle. The common goal of the projects participating in the CRC 974 is to use basic scientific methods in order to gain insight into the mechanisms, communication structures and decision-making processes in the context of liver damage and regeneration, and to investigate the sequelae on other organ systems. A central focus are investigations on the control of liver damage and regeneration by cytokines, growth factors, bile salts, organic osmolytes, mechanosensing, on the immune system, angiogenesis, hepatocyte heterogeneities and on hepatic stellate cells as mesenchymal stem cells and the space of Disse as a stem cell niche. In addition, the importance of bile salt receptors in extrahepatic organs, ammonia handling by the liver and on hepatic encephalopathy on the molecular, cell biological and neurophysiological Level.
DFG Programme Collaborative Research Centres

Completed projects

Participating Institution Universitätsklinikum Essen
 
 

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