ScienceDaily (Sep. 16, 2009) — In a development that could lead to a
novel approach to the treatment of a devastating lung disease, biochemists at
The University of Texas Health Science Center at Houston report they are the
first to link the osteopontin (OPN) protein to chronic obstructive pulmonary
disease (COPD). Findings appear online and will be in the January 2010 print
issue of The FASEB Journal, the journal of The Federation of American Societies
for Experimental Biology.
More than 12 million Americans are currently diagnosed with this incurable
illness, which is the fourth leading cause of death, the National Heart Lung and
Blood Institute reports. In the United States, the term COPD includes two main
conditions - emphysema and chronic obstructive bronchitis.
The researchers were able to prevent COPD features in a mouse model by
genetically removing osteopontin. To gauge the applicability of their findings
to humans, the investigators analyzed the airways of people with COPD and found
elevated levels of the protein.
"This is an important crossover study," said Michael Blackburn, Ph.D., the
study's senior author and professor in the Department of Biochemistry and
Molecular Biology at The University of Texas Medical School at Houston. "Because
we can show osteopontin is elevated in people with COPD, this suggests that
osteopontin could serve as both an indicator of disease progression and a
therapeutic target."
In the study, researchers induced COPD features in mice and then compared
symptoms experienced by mice with osteopontin and those without. The mice
without the protein had less inflammation and lung disease. "The lack of
osteopontin in the mice prevented the COPD features," said Daniel Schneider, the
study's lead author and an M.D./Ph.D. candidate at the UT Health Science Center
at Houston.
"This paper reveals exciting new information on the pathogenetic mechanisms
involved in the development of chronic obstructive pulmonary disease and
emphysema," said Richard J. Castriotta, M.D., professor and director of the
Pulmonary, Critical Care and Sleep Medicine Division at the UT Medical School at
Houston and medical director of the Sleep Disorder Center at Memorial Hermann -
Texas Medical Center.
The study stems from research in Blackburn's laboratory involving a signaling
molecule named adenosine, which can orchestrate the process of inflammation in
wound healing. Adenosine can also activate a cell surface receptor associated
with COPD named A2B and produce osteopontin.
Blackburn's decade-long research has focused on blocking the A2B receptor. With
the new study linking osteopontin to COPD, Blackburn believes his laboratory may
have uncovered a protein that could lead to a more targeted approach to treating
emphysema.
"As a physician scientist, one goal of drug development is to offer more
specific drug targets to treat the disorder and osteopontin provides a specific
target that may be associated with fewer side effects," Schneider said.
"This paper adds a new element, osteopontin, to the mix by discovering its
significant role in the development of COPD with emphysema ... It's still too
early to be used clinically, but there may be a place for osteopontin in the
future as an indicator of lung disease in progress that leads to COPD and
emphysema," Castriotta said.
Blackburn is director of the Graduate Program in Biochemistry and Molecular
Biology at the UT Medical School.
Schneider is a graduate research assistant at The University of Texas Graduate
School of Biomedical Sciences at Houston and is a recipient of a T32 training
grant by the Center for Clinical and Translational Sciences at the UT Health
Science Center at Houston.
The study is titled "Adenosine and osteopontin contribute to the development of
chronic obstructive pulmonary disease." Other contributors from the Department
of Biochemistry and Molecular Biology were graduate students Janci C. Lindsay
and Yang Zhou, as well as senior research assistant Jose G. Molina.
The study was funded by the National Institutes of Health and the National
Center for Research Resources.
Source : ScienceDaily
