Scientists have found out the mechanism of blood flow in liver cells
The liver is divided into sections in which cells perform different tasks, but for a long time it remained unclear how the vessels help maintain this specialization. Researchers have discovered a mechanism linking the movement of blood with molecular signals that determine the functioning of liver cells. How blood flow affects the specialization of liver cells is described in the Izvestia article.
Liver zones: why cells of the same organ work differently
The work of the scientists was published in the scientific journal Nature Communications. Researchers from the Medical Faculty of Mannheim University of Heidelberg and the German Cancer Research Center have studied how blood vessels are involved in the spatial organization of the liver.
The liver performs many functions: it participates in the processing and storage of nutrients, the neutralization of substances and the production of blood proteins. At the same time, hepatocytes — the main liver cells — work differently depending on where they are located inside the liver lobule. This division of functions is called metabolic zonation.
An important role in this process is played by endothelial cells lining the smallest blood vessels of the liver — sinusoids. They emit signals that affect nearby liver cells and help determine their functions.
Blood flow is transformed into molecular instructions
The study was conducted on genetically modified mice. The scientists used single-cell transcriptomics, spatial protein analysis, and biomechanical techniques to trace the relationship between blood movement and vascular cell activity.
It turned out that the endothelial cells of the liver constantly perceive the mechanical forces that arise during the movement of blood. It is these hemodynamic effects that form various molecular programs inside endothelial cells. However, the researchers did not find that such an organization is primarily determined by differences in oxygen concentration or metabolic substances.
Next, vascular cells transmit local signals to neighboring hepatocytes through the Wnt signaling pathway. It is involved in determining the functions of liver cells and their metabolism.
The vessels turned out to be part of the control system
The scientists also discovered that the endothelial cells themselves are spatially organized in such a way as to perceive and transmit these signals.
Kihon Lee, the first author of the study
Endothelial cells act as complex biological interpreters. They read physical information from the bloodstream and convert it into biochemical signals that tell neighboring liver cells what functions they should perform.
Wnt receptors were concentrated in those areas where endothelial cells produced the corresponding signaling molecules. As a result, local signaling chains were formed that support the characteristics of different vascular zones.
Helmut Augustin, senior author of the study
Our work is changing the way blood vessels control organ function. Blood vessels are not passive conduits. They actively measure the mechanical forces generated by blood flow and translate them into molecular instructions that organize the surrounding tissue.
Thus, the physical effect of blood flow is associated with biochemical signals that affect the surrounding cells. Endothelial cells in this system act as intermediaries between the mechanical conditions inside the vessels and the functions of the tissue.
Blood flow signals also affect the vessels themselves.
The discovered mechanism affects not only hepatocytes. The biomechanical program also affects endothelial cells, including their shape and molecular connections with neighboring vascular cells.
The researchers consider the results obtained as an example of how the characteristics of the microenvironment can be transformed into signals that regulate the functioning of tissues. Similar signaling mechanisms between blood vessels and surrounding cells are being studied in other organs, including the heart, lungs, brain, kidneys, and bones.
What can the mechanism provide for the study of liver diseases?
Violation of the normal zoning of the liver is associated with chronic diseases, fibrosis and liver cancer. Therefore, understanding how vascular cells form signals to the surrounding tissue may help to better understand the mechanisms of development of such conditions.
The authors suggest that in the future this knowledge can be used to find approaches aimed not directly at liver cells, but at restoring the normal functioning of the vascular system and its signaling programs. However, the results cannot yet be directly transferred to humans: the study was conducted on mice. Further studies will be required to assess the significance of the discovered mechanism in human liver diseases.
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