Why do liver cells regenerate

Liver renews itself from increased blood flow

The liver is one of the few human organs that regenerates completely within a few weeks if more than half of the organ is removed. The cause of this ability is so far poorly understood. As part of the Collaborative Research Center SFB 974, scientists from the German Diabetes Center (DDZ), together with scientists from Heinrich Heine University (HHU) and Düsseldorf University Hospital (UKD), were able to show for the first time that increased blood flow through the small vessels of the liver Releases signals from the cells of the blood vessels that promote the growth of the liver. The results were published in the current issue of the journal "Nature".

Identified major trigger for organ growth

The liver is one of the most important human organs. On the one hand, it is indispensable for the metabolism, detoxification of the blood and for a functioning immune system. On the other hand, the liver is the only organ that has the ability to completely regenerate its cell mass within a few weeks if more than half of the organ has been removed. The researchers led by Prof. Eckhard Lammert have found that it is the increased blood flow and the mechanical expansion of the blood vessels in the liver that give the liver signals to grow. The signals come from the cells of the blood vessels that respond to the mechanical stimulation. The publication is based on the finding, published in 2001, that blood vessels influence organs in their function and growth (Lammert et al., Science 2001).

“In our study of the liver and its blood vessels, we identified an important trigger for organ growth. For the first time we were able to show that the blood flow and the expansion of blood vessels (vasodilation) release growth-promoting signals, ”explains Prof. Dr. Eckhard Lammert, Director of the Institute for Beta Cell Biology at the DDZ and Head of the Institute for Metabolic Physiology at HHU. "These exciting results could also be of importance in the future for the understanding and treatment of fatty liver diseases in obesity and diabetes," adds Prof. Michael Roden, Scientific Director and Director of the DDZ and Director of the Clinic for Endocrinology and Diabetology at the UKD. "The test results are of great importance for understanding the complex processes involved in liver regeneration and its disorders," emphasizes Prof. Dieter Häussinger, Director of the Clinic for Gastroenterology, Hepatology and Infectiology at the UKD and spokesman for the Collaborative Research Center 974.

Experimental process

The molecular causes of this organ renewal are the subject of a work published by Düsseldorf scientists in the journal "Nature" (Lorenz et al., Nature 2018). Specifically, the scientists were able to show that an increased blood flow through the liver leads to more growth signals being released and activated. One of these signals is the hepatocyte growth factor (HGF), which is particularly important for the growth and survival of liver cells. The endothelial cells of the blood vessels recognize the increased blood flow through the liver with the help of so-called integrins. These are cell surface proteins that connect the extracellular matrix with the cytoskeleton and are capable of other receptors, such as e.g. B. to activate the Vascular Endothelial Growth Factor Receptor-3 (VEGFR3).

The activation of the β1 integrin (a subunit of the integrins) by the increased blood flow leads to the fact that VEGFR3 is activated in endothelial cells and growth factors such as e.g. B. the HGF, activated and released. The latter induce the growth of the liver. As soon as the liver has grown to its normal size and new blood vessels have formed, a normal amount of blood flows through the liver again for each endothelial cell. This normal mechanical stimulation of the endothelial cells could explain why the liver stops growing. The scientists postulate that this molecular mechanism allows the liver to grow as soon as its organ size is reduced and then stops growing when it is restored.

Source: Press release from the German Diabetes Center (DDZ)