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Scientists Identify Gene for Short Circuiting Excess Mucous in Lung Disease, Common Colds
Date:9/14/2009

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 mucous production. SPDEF is an active player in other organ systems that need to produce mucous 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 mucous.

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 mucous in their lungs. In mice where the SPDEF gene was switched off, inflammation and excessive mucous production did not occur, demonstrating the gene's potential as therapeutic or diagnostic target. Mice lacking SPDEF were unable to increase mucous production or develop goblet cells.

In mice where respiratory inflammation and excessive mucous 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 mucous - in particular FOXA3, AGR2 and mucins.

By composition, mucous 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
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SOURCE Cincinnati Children's Hospital Medical Center
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