Role of new pathways in liver regeneration after acute and chronic liver damage

The liver is a vital organ that performs many biological functions (e.g. synthesis of bile and blood proteins, detoxification, glycogen storage, innate immunity). Interestingly, the liver also has a unique ability to regenerate following the loss of liver mass. Loss of at least 30% of liver mass, leads to synchronized proliferation of mature hepatocytes and rapid restoration of liver mass via compensatory hyperplasia.

When a liver has recovered after chronic damage caused by e.g. viral infection the whole complex architecture of the liver must be restored. Hepatic stellate cells (HSCs) are mainly known for their contribution to fibrogenesis in chronic liver diseases, but their role and function in liver regeneration remains unclear.

In summary, both processes are orchestrated by distinct signaling cascades involving components of the innate immune system, cytokines, bile acids and growth factors.

For this reason, our studies aim to investigate the role of different signaling pathways and factors that are essential in both, acute and chronic liver damage. To analyze the dynamic processes during liver regeneration, we performed two common mouse models: PHx (acute liver damage) and BDL (chronic liver damage) in different Knockout-mice with deficiencies in innate immune responses. Using kinetics we examined the gene expression profile of liver tissue after PHx and BDL. H/E-staining of liver sections and cytokine ELISAs were performed and serum protein levels and bile acid concentrations were analyzed.

Taken together, we have found new factors that may be essential for liver regeneration after acute and chronic liver damage, however, their precise role in liver regeneration has to be fully elucidated.

Corresponding author: Behnke, Kristina

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