First Major Difference In
Pulmonary Fibrosis/Scleroderma Between Blacks And Whites Found Using
Physiological Proteomics
SAN FRANCISCO (April 5, 2006) – Of the more than 40,000
persons who die each year in the U.S. from pulmonary fibrosis, the mortality
rate among African-Americans is twice as high Caucasians.
A physiologist from Belarus who’s worked at the Medical
University of South Carolina for almost 10 years thinks she’s found a
mechanism that could explain why.
“Pulmonary fibrosis is a deadly, very complex disease
where the lung’s air sacs are replaced by tough fibrotic tissue,” Galina
Bogatkevich said. Using modern physiological technology called proteomics,
Bogatkevich’s laboratory compared healthy and diseased lung fluid and found
that a key growth factor that is supposed to inhibit fibrotic growth is
malfunctioning.
“This is the first time we’ve identified a
physiological difference that parallels the profound differences between
black and whites in the severity of the disease and prognosis,” she said in
an American Physiological Society session at Experimental Biology in
San Francisco.
*Paper presentation: “Antifibrotic effect of
hepatocyte growth factor is impaired in lung fibroblasts isolated from
African-Americans,” APS Physiology Airway Mechanics and
Mechanotransduction in the Lung 767.9/board #C684. Research was by
Galina Stephanie Bogatkevich, Anna Ludwicka-Bradley, D. Beth Singleton and
Richard M. Silver, Department of Medicine, Medical University of South
Carolina, Charleston.
Proteomic approach finds lowered antifibrotic HGF
among black patients
Pulmonary fibrosis (PF) strikes nine of out 10 patients
with systemic sclerosis or scleroderma, a group of diseases involving
abnormal growth of the connective tissue that supports the skin and internal
organs. Current thinking is that pulmonary fibrosis is caused by micro
injury to the lung as part of the earlier diseases’ progress.
“But we also know that PF is a ‘proteomic disease’ –
that is its pathogenesis depends on the imbalance in expression and
communication between many proteins,” Bogatkevich noted. Using the proteomic
approach they found that the amount of antifibrotic glycoprotein hypatocyte
growth factor (HGF) was reduced in the blood and epithelial lining fluid of
African-American scleroderma patients than in Caucasians.
And the latest study presented in San Francisco
“demonstrates that antifibrotic effects of HGF are impaired in lung
fibroblasts isolated from Africa-Americans may be due to the deficiency in
c-Met receptor function,” Bogatkevich said. “This may explain, in part, the
greater severity and worse prognosis for African-American scleroderma
patients.”
Until now the only therapy for this very difficult
group of diseases was palliative: oxygen to increase the chance of breathing
success and/or trying to generally boost the immune system. Neither approach
is real therapy,
Next steps
However, “now that we’ve identified the c-Met
malfunction, it gives us a good direction to follow,” Bogatkevich said.
“It’s a promising target that seems to take the same clear track as the
disease’s population.”
First step is “we need to find or develop a suitable
animal model where PF can be imposed. Also we plan to do polymorphism
studies because probably there are some Whites that have differences in the
c-Met function due to damage or signaling difficulties and the results could
give us some useful clues.”
She said it’s also possible “now that we know what to
study, that further work on scleroderma itself will be more productive. It’s
a little simpler disease, and since PF develops from these diseases in the
first place, going upstream in the pathogenesis could yield even more useful
results. These future studies on the c-Met receptor functionality definitely
will advance out understanding of this range of diseases,” Bogatkevich
concluded.
Funding: Scleroderma Foundation, National Institutes
of Health.
* * *
Editor’s Note: For
further information or to schedule an interview with a member of
the research team, please contact Donna Krupa at the APS newsroom @
415.905.1024 (March 31-April 5); or (703) 967-2751 (cell) or (301) 634-7209
(office),
dkrupa@the-aps.org; or Christine Guilfoy at 978.290.2400 (cell) or
301.634.7253 (office).
* * *
The
American Physiological Society was founded in 1887 to foster basic and
applied bioscience. The Bethesda, Maryland-based society has more than
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 May 2004, APS received
the Presidential Award for Excellence in Science,
Mathematics and Engineering Mentoring (PAESMEM).
# # #
A searchable
online program for EB is at
http://www.faseb.org/meetings/eb2006/call/default.htm
Experimental Biology is an annual
scientific meeting convened by the Federation of American Societies of
Experimental Biology, including the American Physiological Society (APS)
and other biomedical societies. The meeting features “nominated” lectures,
symposia, research presentations, awards, a job placement center, and an
exhibit of scientific equipment, supplies, and publications. This year’s
participating Societies are APS, American Association of
Anatomists, American Society for Biochemistry and Molecular Biology,
American Society for Investigative Pathology, American Society for
Nutritional Sciences, and the American Society for Pharmacology and
Experimental Therapeutics.
