In mammals, the liver can repair and regenerate after damage or injury through at least two biochemical pathways. Now scientists have identified genes that are crucial to liver regeneration; some are regulatory genes, while others are directly involved in the regenerative process. The findings, which were reported in Cell Genomics, have provided new insights into tissue repair that could have implications for regenerative medicine.
In this work, the researchers used a mouse model to study the mechanisms that were activated by removing part of the liver. The study focused on how the organization of DNA changed, which can expose different parts of the genome for activation; and how these changes were related to liver regeneration.
Liver transplant surgery, or the removal of liver tumors is a common procedure, "so understanding how this process works can help to design strategies that optimize its response," said senior study author Montserrat Corominas of the Institute of Biomedicine of the UB (IBUB).
The investigators also compared liver regeneration to processes of liver development in the embryo, to look for similarities.
The work identified certain genes that are critical for liver regeneration, including regulatory genes that enhance the expression of other genes. These regulatory genes affected other genes that are related to regeneration, and triggered certain enhancers that are typically active during development. Ultimately, this resulted in the growth and proliferation of the most common cell type in the liver, which are known as hepatocytes.
Other regulatory elements in the genome that are related to normal liver function were also repressed during regeneration. The metabolism of lipids was particularly diminished.
"This reveals that regeneration is a highly regulated process in which an inverse relationship is established: These proliferation programs are prioritized while energy-intensive metabolic processes, such as the synthesis of bile acids and retinols, are temporarily inhibited," said first study author Palmira Llorens-Giralt of IBUB.
This work has revealed a kind of map of interactions between enhancers and genes during liver regeneration. While this study does not translate into clinical applications, it informs studies that might, like drugs that can trigger these pathways, and activate liver regeneration, such as in patients of liver disease.
Sources: University of Barcelona, Cell Genomics