Scientists at Cincinnati Children's Hospital Medical Center have identified a gene that causes excessive mucous in the lungs. Their research also turns certain beliefs about how certain cells promote chronic lung infection and excess mucous production on their head. Results appeared in the September 14 issue of The Journal of Clinical Investigation.
Scientists previously thought that after airways were attacked by an allergic response or inflammation, mucous cells (known as goblet cells) divided and proliferated at a very fast rate, a process called hyperplasia. Instead, the Cincinnati Children's team discovered that beneficial lung cells called Clara cells change their cell type to become goblet cells in a process called metaplasia. They also found the metaplasia process in this instance to be reversible.
The study identified transcription factor SPDEF as a gene that regulates a chain 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 that the gene is mostly quiet.
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.
The researchers report that SPDEF turned off genes involved in biological processes that help protect lung tissues from infection and damage. Conversely, it activated genes that promote inflammation and excessive mucous, in particular FOXA3, AGR2, and mucins.
AGR2, for example, helps assemble mucous proteins by folding together different molecules. When SPDEF is overexpressed, it results in increased production of AGR2, which in turn promotes an over-abundance of protein folding and mucous production.
In mice where the SPDEF gene was switched off, inflammation and excessive mucous production did not occur. Mice lacking SPDEF were unable to increase mucous production or develop goblet cells.