Featured Research

from universities, journals, and other organizations

Scientists Identify Gene For Short-circuiting Excess Mucus In Lung Disease, Common Colds

Date:
September 15, 2009
Source:
Cincinnati Children's Hospital Medical Center
Summary:
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 disease or just those fighting the common cold. The discovery sheds light on the precise biological reasons the lungs in people with asthma, cystic fibrosis and other respiratory ailments clog with thick mucus.

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.


Story Source:

The above story is based on materials provided by Cincinnati Children's Hospital Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Chen et al. SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production. Journal of Clinical Investigation, 2009; DOI: 10.1172/JCI39731

Cite This Page:

Cincinnati Children's Hospital Medical Center. "Scientists Identify Gene For Short-circuiting Excess Mucus In Lung Disease, Common Colds." ScienceDaily. ScienceDaily, 15 September 2009. <www.sciencedaily.com/releases/2009/09/090914172332.htm>.
Cincinnati Children's Hospital Medical Center. (2009, September 15). Scientists Identify Gene For Short-circuiting Excess Mucus In Lung Disease, Common Colds. ScienceDaily. Retrieved August 27, 2014 from www.sciencedaily.com/releases/2009/09/090914172332.htm
Cincinnati Children's Hospital Medical Center. "Scientists Identify Gene For Short-circuiting Excess Mucus In Lung Disease, Common Colds." ScienceDaily. www.sciencedaily.com/releases/2009/09/090914172332.htm (accessed August 27, 2014).

Share This




More Health & Medicine News

Wednesday, August 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Predicting Heart Transplant Rejection With a Blood Test

Predicting Heart Transplant Rejection With a Blood Test

Ivanhoe (Aug. 27, 2014) Now a new approach to rejection of donor organs could change the way doctors predict transplant rejection…without expensive, invasive procedures. Video provided by Ivanhoe
Powered by NewsLook.com
Better Braces That Vibrate

Better Braces That Vibrate

Ivanhoe (Aug. 27, 2014) The length of time you have to keep your braces on could be cut in half thanks to a new device that speeds up the process. Video provided by Ivanhoe
Powered by NewsLook.com
Smartphone App Tracks Your Heart Rate

Smartphone App Tracks Your Heart Rate

Ivanhoe (Aug. 27, 2014) A new app that can track your heart rate 24/7 is available for download in your app store and its convenience could save your life. Video provided by Ivanhoe
Powered by NewsLook.com
Stroke in Young Adults

Stroke in Young Adults

Ivanhoe (Aug. 27, 2014) A stroke can happen at any time and affect anyone regardless of age. This mother chose to give her son independence and continue to live a normal life after he had a stroke at 18 years old. Video provided by Ivanhoe
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins