Genetic Link between Smoking and COPD
University of Iowa researchers have found what they believe is the first
link between smoking and decreased expression of a new class of noncoding
RNAs (microRNAs) in smokers' immune cells.
"Only 20 percent of smokers get COPD (chronic obstructive pulmonary disease)
but no one knows why," says Martha Monick, Ph.D., professor of internal
medicine at the University of Iowa Roy J. and Lucille A. Carver College of
Medicine. "This discovery identifies changes in a new class of molecules,
microRNAs, that might be driving gene expression that ultimately leads to
COPD/emphysema and other smoking-related disorders."
Additionally, Monick says the discovery identifies specific smoking altered
microRNAs that may provide future therapeutic targets.
The study, which looks at microRNA and gene expression in lung immune cells,
was published online recently in the journal PLoS ONE at
http://dx.plos.org/10.1371/journal.pone.0044066. Monick is co-senior author
with Mary Wilson, M.D., UI professor of internal medicine and microbiology.Joel Graff, PhD, a research scientist in Wilson's laboratory, is primary
author, and Thomas Gross, M.D., UI associate professor of internal medicine,
is a co-author and oversees the clinical aspects of the research.
According to Monick, the new research identifies changes in microRNAs, a new
class of gene expression regulators, in cells from smokers' compared to
nonsmokers' lungs. It is the first study to demonstrate significant
down-regulation of these small noncoding RNAs (microRNAs) in lung
macrophages from smokers. Macrophages are critical components of the innate
immune system and changes in these cells are strongly linked to disease
development.
In addition, the study links changes in a specific microRNA (miR-452) to
increased production of a protein-degrading enzyme called MMP12, long
associated with the development of COPD and emphysema. This research, she
says, identifies a novel biological mechanism (changes in microRNA
expression controlling disease relevant genes) that may be playing an
important role in smoking-related diseases.
"We discovered the massive down-regulation of microRNAs with smoking and and
are continuing to study the mechanism of that down regulation. We are also
working to identify specific microRNAs, like the one we have linked to
MMP12, that alter expression of genes involved in smoking-related diseases."
Monick says.
