This is what happens to us when the liver loses its identity

This is what happens to us when the liver loses its identity

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Since we studied Natural Sciences at school, we all assimilate that inside our body there are a series of organs that fulfill a very specific range of functions. What is the first example that comes to mind? Perhaps the heart, to pump blood, or the lungs, responsible for breathing. But has any reader thought of the liver first? Surely not, even though it is a key organ for our survival.

The liver is a central regulator of the body’s metabolism. Hormones and coagulation factors are made in it, energy is stored, bile salts are produced to digest fats, cholesterol and blood glucose levels are regulated, vitamins and minerals are stored, and the blood is cleaned of toxins, including drugs, drugs or other harmful substances.

cells become specialized

Our body is made up of approximately 30 trillion cells, which are grouped in an organized way into tissues and later into organs. The cells that make up each organ are specialized to perform a series of very specific tasks.

To make matters worse, in each organ there are different types of cells with different functions but a common goal. His thing is teamwork.

Thus, for example, in the brain we find mainly neurons and astrocytes, in the heart cardiomyocytes, in the skin keratinocytes and melanocytes, and in the liver we find hepatocytes and cholangiocytes.

Although all the cells in our body contain an exact copy of the same genes, some cells use some genes and others others.

To understand it better, let’s think of genetic material as a storehouse of DIY tools and genes as each of these tools. The different guilds construction workers carry a toolbox with the material they need to carry out their function. Moreover, these tools identify them. In this way, the toolbox of a plumber will be different from that of a carpenter, which in turn will be different from that of an electrician.

In the organism, between the whole set of genes (the same common warehouse), each cell specializes using specific genes (its Toolbox), which differentiate it from the rest. What in working life we ​​call professional specialization, in biology we call cell differentiation.

The warehouse manager of the liver

For the most part, genes are used to make the proteins that cells use to carry out their functions. Also, some of these proteins decide which genes pass and which don’t to protein.

In the liver, for example, there is a protein that acts in this way called HNF4α. It depends on which genes involved in the different functions performed by the liver are used, thus giving identity to hepatocytes.

It is a hierarchical regulation and, following the previous simile, HNF4α would be the storekeeperthe person who distributes the tools according to the tasks to be carried out.

When does the liver lose this identity?

The liver can be damaged for different reasons. Acutely due to intoxication by drugs, alcohol or toxins. Chronically when any of these aggressions in more moderate doses persist over time, or when excessive fat accumulates or infections by hepatitis B and C viruses occur, for example.

In these situations, many hepatocytes die and the rest lose the ability to carry out their functions because they have lost their identity, they become disdifferentiate. This is when patients begin to manifest the symptoms of the disease.

How does this happen? Our research group has identified that the protein called SLU7 is decreased in the liver of patients. In addition, we show that SLU7 is essential in the healthy liver to maintain its functions, controlling the use of many other genes.

More recently we have shown that SLU7 is the equivalent of warehouse manager of DIY tools. From its top level in the hierarchy, SLU7 is required for HNF4α to remain in hepatocytes, preserving their function and identity.

So that we understand it, if the boss suddenly gets sick and does not come to work, that is, the amount of SLU7 decreases, the rest of the workers lose their place and do not know what to do.

In short, the function and identity of our cells depends on the correct use of the information contained in our genes. In certain circumstances, this identity is lost and, as a result, we get sick.

As researchers, we intend to identify which genes or proteins are failing so that, when that happens, we can return its lost identity to the liver as soon as possible.


This article was a finalist in the II edition of the youth disclosure contest organized by the Lilly Foundation and The Conversation Spain.


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