Molecular events involved in liver regeneration
The ability to regenerate after major tissue damage or surgical intervention is an important property of the liver. Since liver resection is an established therapeutic measure for severe liver diseases, it would be of importance to know which molecular events underly the regenerative process and if they depend on the extent of resection, as indicated in previous studies. The group led by Prof. Schlaak from the Department of Gastroenterology and Hepatology of the University Hospital of Essen compared rats undergoing 70% and 90% liver resection. Serum parameters, activation of transcription factors, expression of cytokines known as imperative for the start of liver regeneration and apoptosis in the regenerating liver tissue were analyzed. A broad spectrum of methods came into use, including quantitative real time PCR on mRNA-isolates and TUNEL staining of histological samples. This will be published on December 14, 2008 in the World Journal of Gastroenterology.
They found that apart from increased liver damage and reduced liver function parameters found in serum samples, molecular events as cytokine expression, especially IL-6 and TNF-alpha were strongly reduced after extensive resection. In addition the activation of NF-kappa B was delayed by almost 24 h. Programmed cellular death, known as apoptosis, was partially increased at 24 h and at 7 d postoperatively in the livers of animals which underwent 90% resection in comparison to rats which only had 70% of their liver resected.
The findings show clearly that extended liver resection leads to a delay of regeneration. This is not only a reduction of the regenerative capacity due to a smaller amount of cells or tissue. The data presented by Prof. Schlaak´s group suggest an impaired ability of the liver to regenerate on a molecular and cellular level. This seems to involve signalling of NF-kappa B and maybe highly conserved TLR systems. Upcoming projects of the research group already adress this possibility.
Further knowledge about the interrelation of liver regeneration and the molecular events involved may yield new approaches to improve patient outcome after extended hepatectomies or to make surgical intervention available for patients who could not undergo a liver resection due to severe previous liver damage.