Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists identify gene for short-circuiting excess mucus in lung disease, common colds

15.09.2009
Scientists have identified the main genetic switch that causes excessive mucus in the lungs, a discovery that one day could ease suffering for people with chronic lung diseases like asthma and cystic fibrosis, or just those fighting the common cold.

The discovery was reported in a study posted online Sept. 14 by the Journal of Clinical Investigation. The new research sheds light on what has been a medical mystery - the precise biological reasons that the lungs in people with asthma, cystic fibrosis and other respiratory ailments clog with thick mucus.

Identifying the genetic circuits that cause mucous hyper-production gives researchers potential targets for new therapies to moderate or stop it, said Jeffrey Whitsett, M.D., the head of Neonatology, Perinatal and Pulmonary Biology at Cincinnati Children's Hospital Medical Center and the study's senior investigator.

"Everyone has had a stuffed up nose and cough after two or three weeks of a bad cold and most over-the-counter cold medications deal with mucus," Whitsett explained. "We still don't have effective therapies for removing excess mucous, whether it's someone with a cold or chronic lung disease. That's why we still tap on the chests of kids with cystic fibrosis to try and clear it."

The current study provides an entirely new understanding of how certain cells promote chronic lung infection and excess mucus production. Scientists previously thought that, after airways were attacked by an allergic response or inflammation, mucus cells (known as goblet cells) divided and proliferated at a very fast rate - a process known as hyperplasia. Instead, the Cincinnati Children's team discovered that beneficial lung cells, called Clara cells, instead change their cell type to become goblet/mucous cells in a process called metaplasia.

Dr. Whitsett and his colleagues also found the metaplasia process in this instance to be reversible. Goblet cells can change back to Clara cells if the detrimental genetic influence is blocked, highlighting a possible pathway for new treatments, according to Dr. Whitsett, who also is executive director of the Perinatal Institute at Cincinnati Children's.

The study identifies a transcription factor, SPDEF, as the master gene that regulates a chain of dozens of downstream genes involved in mucus production. SPDEF is an active player in other organ systems that need to produce mucus for normal function, such as the digestive system. In healthy lungs, however, the researchers report the gene is mostly quiet, as healthy lungs don't produce significant amounts of mucus.

Using an egg white protein called ovalbumin to induce an allergic reaction and inflammation in the lungs of mice, the researchers observed a dramatic elevation in the expression of SPDEF in the lung tissues of the affected animals. The animals also experienced hyper-production of thick mucus in their lungs. In mice where the SPDEF gene was switched off, inflammation and excessive mucus production did not occur, demonstrating the gene's potential as therapeutic or diagnostic target. Mice lacking SPDEF were unable to increase mucus production or develop goblet cells.

In mice where respiratory inflammation and excessive mucus production were present, the researchers report that SPDEF turned off genes involved in biological processes that help protect lung tissues from infection and damage. Conversely, SPDEF activated genes that promote inflammation and excessive mucus - in particular FOXA3, AGR2 and mucins.

By composition, mucus is a sugar-coated collection of large proteins that, in healthy conditions, help the body defend itself by collecting and then clearing out contaminants. In the case of AGR2 for example, the gene helps assemble mucus proteins by folding together different molecules. When SPDEF is over-expressed, it results in increased production of AGR2, which in turn promotes an over-abundance of protein folding and mucus production.

Dr. Whitsett cautioned it will be several years before the research results in a specific therapeutic approach that can be tested in people. In the meantime, his team has received several significant grants to conduct more extensive studies into the various genetic and molecular influences that control, or are controlled by, SPDEF and involved in excess mucus production.

The first author on the current study was Gang Chen, a graduate student in Dr. Whitsett's laboratory. The laboratory's research is supported by funding from the National Institutes of Health and the Cystic Fibrosis Foundation. The study was done in collaboration with the Netherlands Institute of Developmental Biology, with the research there being led by Dr. Hans Clevers.

About Cincinnati Children's

Cincinnati Children's Hospital Medical Center is one of 10 children's hospitals in the United States to make the Honor Roll in U.S. News and World Reports 2009-10 America's Best Children's Hospitals issue. It is #1 ranked for digestive disorders and is also highly ranked for its expertise in respiratory diseases, cancer, neonatal care, heart care, neurosurgery, diabetes, orthopedics, kidney disorders and urology. One of the three largest children's hospitals in the U.S., Cincinnati Children's is affiliated with the University of Cincinnati College of Medicine and is one of the top two recipients of pediatric research grants from the National Institutes of Health.

President Barack Obama in June 2009 cited Cincinnati Children's as an "island of excellence" in health care. For its achievements in transforming health care, Cincinnati Children's is one of six U.S. hospitals since 2002 to be awarded the American Hospital Association-McKesson Quest for Quality Prize for leadership and innovation in quality, safety and commitment to patient care. The hospital is a national and international referral center for complex cases. Additional information can be found at www.cincinnatichildrens.org.

Nick Miller | EurekAlert!
Further information:
http://www.cchmc.org

More articles from Health and Medicine:

nachricht One gene closer to regenerative therapy for muscular disorders
01.06.2017 | Cincinnati Children's Hospital Medical Center

nachricht The gut microbiota plays a key role in treatment with classic diabetes medication
01.06.2017 | University of Gothenburg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>