Strand of DNA under a magnifying glass and shaped like a question mark

Researchers Home in on Possible Cause of Emphysema

Researchers in Japan have stumbled upon an interesting discovery. They think they have discovered a protein responsible for the early stages of emphysema, and the hope is this will someday lead to an effective treatment. Here is what to know.

Learning about genes

The human genome project was started in the early 1990s. About 20 years later, researchers reported that they had identified every human gene. They discovered that there are between 20,000 and 30,000 genes that make proteins. It is breakdowns in these genes, they think, that are responsible for many of the diseases that plague mankind, including emphysema.1-2

Each of these genes plays a role in how your body functions. For instance, immune genes tell immune cells what to do and this is how your body stays free of germs and infections. For our sake, it is how our lungs stay healthy.

It is rare, but sometimes changes occur to human genes. When changes occur to genes they are said to be gene variations or mutations. One way for genes to mutate is when they are exposed to substances in the environment. A good example of such a substance is cigarette smoke.1-2

Mutated immune genes

I shall give you an example. COPD genes are immune genes that have mutated. One such example is a gene called Matrix Metalloprotease 12 (MMP12). This is one of many genes responsible for your immune system. It makes a protein called MMP12. This protein controls the activity of an enzyme called elastase. Elastase is responsible for the breakdown of elastin.3-4

I'm sure we're all familiar with elastase. Right? It's what your air exchange units called alveoli are made of. Alveoli are balloon-like structures inside your lungs. Their walls are made of elastin. It's a flexible substance that allows alveoli to expand when you inhale and recoil when you exhale. It's the substance that helps alveoli maintain their shape.

So a mutated MMP12 gene promotes the breakdown of elastin and other lung tissue. It causes lung cell death and inflammation of lung tissue. This is what scientists believe causes emphysema. But, what is it that triggers this entire process? Up until now, the answer remained unknown.4

Our latest discovery

Researchers have long been aware of an immune gene called FCHSD1. It is a gene that makes a protein called FCHSD1. Until recently researchers were uncertain what exactly this protein was responsible for.6-8

However, after performing their study in Japan, researchers now think this protein may be responsible for initiating the process I described above in my example. They think this protein may be responsible for the early stages of emphysema.7-8

To make this discovery, researchers in Japan performed experiments on mice. They had two groups: one group was missing the FCHSD1 protein and the other group had “normal” levels of this protein. In both groups, they injected elastase. This is the substance noted above that induces emphysema. Then, over time, they compared the results in both groups.7-8

  • Normal FCHSD1 protein levels. This group had elevated FCHSD1 protein levels. They had evidence of lung cell death and lung tissue inflammation. This group developed emphysema.
  • Missing FCHSD1 protein. This group had no evidence of lung cell death and no lung tissue inflammation. They did not develop emphysema.

The study results seem to indicate that the FCHSD1 protein causes lung cells to die, and perhaps causes lung tissue inflammation. This is what eventually leads to emphysema.

How might FCHSD1 cause emphysema?

Researchers have a theory. They think another gene involved here is the NRF2 Gene. This gene makes a protein is called NRF2 which is a protein that responds to stress. Cigarette smoke is one substance that causes stress inside your lungs. In healthy lungs, researchers think NRF2 moves to the nucleus of cells. This helps defend the cell against stress.7

So, what happens if FCHSD1 is present? Researchers think FCHSD1 binds with NRF2, thereby preventing it from moving into the nucleus. So FCHSD1 prevents NRF2 from defending the cell from stress. This causes oxidative stress which initiates an immune response that causes cell death, tissue inflammation, and emphysema.7

On the contrary, FCHSD1 deficiency inhibits the development of emphysema. When FCHSD1 is not present, NRF2 is able to move to the nucleus freely when the cell is under stress. This prevents the development of emphysema.6

Of course, this data was obtained from mice. Would this same effect occur in humans as well? To answer this question further studies are indicated.

This brings us hope

Researchers have learned a lot since the early 1990s. They have identified the entire human genome. They have identified what proteins are made by each gene. And now they are learning which genes/protein combinations might play a role in diseases like emphysema. The hope is further studies here will lead to future treatment options.

One future medicine may enhance the effects of NRF2. Another future medicine may inhibit or block the effects of FCHSD1. And yet another may do both. One hope is that such medicine will prevent future generations from getting emphysema. The other hope is that it will treat, and maybe even cure, emphysema in those already diagnosed.

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