Lungs Try To Repair
Damaged Elastic Fibers
FORT LAUDERDALE, Fla. (Nov. 3, 2006) _ The lungs of
patients suffering chronic obstructive pulmonary disease (COPD) attempt
to repair damaged elastic fibers, a new finding that contradicts the
conventional wisdom on the capabilities of the adult lung.
The study “Evidence for attempted regional elastic
fiber repair in severe emphysema,” was done by Jason Woods, Kristin
Castillo, Alexander Patterson and Richard Pierce of Washington
University, St. Louis, Mo.; Joel Cooper of the University of
Pennsylvania, Philadelphia; and James Hogg of St. Paul’s Hospital,
Vancouver, British Columbia. The authors will be present their findings
Nov. 3 at The American Physiological Society conference
“Physiological Genomics and Proteomics of Lung Disease.”
The researchers found that synthesis of elastin, a
gene linked to elastic fiber growth, is increased in the moderately
diseased tissue of COPD patients. Elastic fibers allow the lung to
expand and contract with breathing.
“We’ve found elastin synthesis to increase in the
air sacs (alveoli) and airways of the lungs of patients suffering severe
or end-stage COPD,” Woods explained. “This shows that the lung may be
attempting to repair itself.”
The finding is important because it could pave the
way to develop a drug to ‘turn on’ key genes to allow the lung to grow
new alveoli, he said. Alveoli play a role in the exchange of oxygen and
carbon dioxide between the lungs and the circulatory system.
A 2-year-old could do
it
Very young children who suffer lung injuries
increase elastin expression and produce new elastic fibers inside the
alveoli, Woods said. Adults do not have that ability and that has led
physiologists to conclude that the elastin gene must shut off after we
reach a certain age, ending elastin fiber production.
Physiologists want to understand this process in
the hope that it could be harnessed to repair the diseased adult lung.
In particular, Woods and his colleagues looked at three genes associated
with elastic fiber assembly: Emilin-1, MFAP2 and elastin. They found the
expression of elastin consistently increased in the diseased lungs they
studied.
In a preliminary study, the researchers examined
two diseased lungs removed from end-stage COPD patients undergoing lung
transplants. COPD develops as a result of exposure to toxins such as
cigarette smoke, resulting in inflammation to the small airways and
destruction of elastic fibers within alveoli. The patients suffered from
emphysema.
The team used hyperpolarized magnetic resonance
imaging (MRI) to characterize the regions of the lung showing moderate
emphysema and regions showing severe emphysema. They found that new
elastin synthesis was initiated in moderately diseased specimens.
The researchers did a second study using 10 lungs
from end-stage COPD patients who had undergone transplants. Again, they
found the greatest amount of elastin gene expression in the moderately
diseased areas of the lungs, Woods said. There was no variability in
elastin levels within the control lungs.
Further, the team found that the increase in
elastin expression occurred on the alveolar walls, the same area where
elastin occurs during the lung’s development in children. This shows the
lung is attempting to repair the elastic fibers in end-stage emphysema,
the authors concluded.
Funding
National Institutes of Health (Pierce) and the
Barnes-Jewish Foundation (Woods)
* * *
The
American Physiological Society was founded in 1887 to foster basic and
applied bioscience. The Bethesda, Maryland-based society has 10,500
members and publishes 14 peer-reviewed journals containing almost 4,000
articles annually.
* * *
APS
provides a wide range of research, educational and career support and
programming to further the contributions of physiology to understanding
the mechanisms of diseased and healthy states. In 2004, APS received
the Presidential Award for Excellence in
Science, Mathematics and Engineering Mentoring.
