First Different Black/White Mechanism In Pulmonary Fibrosis/Scleroderma Identified

[Guest guest]

Source: American Physiological Society

Posted: April 5, 2006

First Different Black/White Mechanism In Pulmonary Fibrosis/

Scleroderma Identified

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 Bogatkevich,

Ludwicka-Bradley, D. Beth Singleton and M. Silver, Department

of Medicine, Medical University of South Carolina, ton.

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.

http://www.sciencedaily.com/releases/2006/04/060405022510.htm