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New starting point for the treatment of chronic lung diseases discovered
Our respiratory tract contains the finest cilia, which move back and forth in a protective film of mucous membrane, transporting dust, foreign bodies and pathogens in the direction of the nasopharynx. If these hairs can no longer fulfill their task, severe respiratory tract infections and respiratory complaints such as chronic obstructive pulmonary disease (COPD) develop. So far, however, it was unclear how it actually comes to a defect of cilia on the genetic level. Now it is an international research team headed by the Göttingen scientist dr. Muriel Lizé has managed to identify a specific protein that may be responsible for the defect. The research results were published in the journal "Genes & Development".
Fine cilia remove pollutants
Every day we breathe in and out about 20,000 times. With every breath we take on the vital oxygen, but at the same time also many tiny particles ("fine dust"), irritating pollutants and tiny pathogens (bacteria, fungi or viruses) can get into the respiratory tract. In order to protect the organs from the harmful substances, the entire respiratory system - apart from the throat, epiglottis and vocal cords - is lined with a mucous membrane, which consists of a special cell layer. The cells of this so-called "ciliated epithelium" are equipped on the surface with fine cilia (cilia), which continuously perform rhythmic strokes and thereby move liquid. Small dust particles or bacteria stick to the wet mucous membrane and are thus transported away from the cilia in the direction of the pharynx and finally swallowed automatically.
Scientists have discovered a potential key gene for the treatment of chronic lung disease. (Image: magicmine / fotolia.com) International research team identifies special protein
In certain diseases such as the so-called "primary ciliary dyskinesia (PCD)", the functionality of the cilia is limited, the University of Göttingen (UMG) reported in a recent press release. This is a relatively rare condition in which the dysfunction is genetic and causes fluid to accumulate and foreign bodies or pathogens to move. As a result, chronic respiratory tract infections and severe respiratory problems, such as the so-called "chronic obstructive pulmonary disease" (COPD), which is colloquially also referred to as "smoker's lung" or "smoker's cough".
But these diseases still raise questions in science, because It is unclear how exactly at the level of the genes a defect of the cilia occurs, the report says. Now, however, an international team of researchers led by the Göttingen scientist dr. Muriel Lizé apparently identified a specific protein that regulates a network of genes responsible for the formation of cilia in cells. The new findings may, according to scientists, contribute to a better understanding of the causes of chronic lung disease in humans.
Mice show symptoms like rare respiratory disease
The researchers found that the cause of a possible cilia defect was discovered by observation in an animal experiment. The team realized that in mice with a genetic defect that was not yet associated with PCD, typical symptoms of the disease still occurred. It turned out that in these animals that gene was mutated, which provides the blueprint for the protein p73, the report goes on. This is mainly known to protect the organism from cancerous degeneration and to participate in developmental processes.
"Mice without functional p73 show a variety of symptoms that could not be explained with the previously known functions of p73," said the head of the Molecular Oncology and Experimental Pulmonology group at the Institute of Molecular Oncology and the Department of Cardiology and Pneumology, University Medical Center Göttingen (UMG ), Dr. Lizé. Further studies revealed that mice lacking this protein suffered from runny nose, sinus infections, and emphysema.
Completely stunted ciliated epithelium
"All these are symptoms that we know from mice in which the cilia are not fully functional," said the molecular biologist. Under the microscope, the scientists recognized massive changes in the respiratory apparatus of the animals. "The ciliated epithelium was completely stunted, we found almost no cilia. And the few available were significantly shortened, "Dr. Dietmar Riedel from the Max Planck Institute for Biophysical Chemistry in Göttingen, quoted in the communication.
Cells without p73 emit less cilia
To find out if the protein p73 is indeed the cause of the defective hair, they bred epithelial cells from the respiratory tract of mice in the test tube and made them by a special stimulus to form cilia. Again, the same pattern was seen in the respiratory tract of the mice: the cells without the protein developed significantly fewer and shorter cilia than those with functional p73.
The lack of the protein had therefore apparently directly affected their expression and thereby triggered the serious respiratory diseases. A real surprise for the researchers, "because so far the protein p73 had never been linked to a function in the respiratory tract," says Dr. Lizé.
New starting point for improved therapies
In addition, the team from Göttingen explored the importance of the protein in the development of cilia. On the basis of previous findings, the researchers assumed that p73 regulates the formation of these by influencing certain genes. In cooperation with the research group of Dr. med. Stefan Bonn from the German Center for Neurodegenerative Diseases (DZNE), the experts were able to identify more than 50 genes that were controlled by p73 and are directly important for the growth of the hair. This included the so-called "Factor FoxJ1", which is considered to be the central regulator of cilia, according to the information from the university.
"With p73 we have identified a factor that controls a whole network of genes that are important for a functioning ciliated epithelium. This provides a new starting point for developing and improving therapies for diseases such as PCD and COPD. " Lizé. (No)