Sydney researchers have discovered how a specific protein causes scar tissue to be made in the lungs of asthmatic patients.
This finding could be used in the treatment of asthma by developing new drugs to target scar tissue formation and thereby assist asthmatics who have trouble breathing.
“Scar tissue is a major contributor during an asthma attack. It builds up inside the airways and makes it hard for asthmatics to breathe by reducing the amount of air that can get into the lungs,” says Dr Janette Burgess, from the Woolcock Institute of Medical Research at the University of Sydney and a 2003 Fresh Science presenter.
“The scar tissue is a bit like cholesterol building up inside an artery. It makes the space available to let in air much smaller so it is much harder to get it in,” she says.
“Current treatments for asthma cannot prevent this scar tissue build up,” says Janette.
Janette and her team made this discovery by growing human airway smooth muscle cells from asthmatic and non asthmatic volunteers in dishes in the laboratory at the University of Sydney. “We showed that the asthmatic cells produced 20 times more of this scar creating protein, called connective tissue growth factor” she says.
Since this research was published, Janette’s group have also shown a similar increase in scar-creating protein in airway segments from human lung.
“And we have discovered that asthmatics are missing a natural substance which normally controls scar tissue formation. This means the balance between scar creating protein and stop protein is disrupted,” says Janette.
In Australia as in other Western nations, asthma has a major community impact. One in four children and one in ten adults have asthma which costs our community between $585-$720 million per annum. According to the Asthma Foundation (NSW), in 2001, 422 people died from asthma in Australia.
Janette’s research was published in American Journal of Respiratory and Critical Care Medicine (Vol 167, pages 71-77).
On Tuesday and Wednesday Janette will be presenting her work to the public at the Great Australian Science Show at the Melbourne Museum along with 15 other Fresh Scientists selected from over 100 nominations.
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NH&MRC Peter Doherty Fellow Woolcock Institute of Medical Research, University of Sydney
Asthma linked to scar creating protein
Discovery of what induces scar tissue in the lungs of asthma patients
Asthma is a major burden in Australia – affecting 25% of children and 10% of adults. Scar formation in the lungs of asthmatics is a major contributor to difficulty in breathing during an asthma attack. I have discovered what causes the scar tissue to be made. This finding could be the key to new drugs for the treatment of asthma.
I have recently discovered that a new protein called connective tissue growth factor (CTGF) causes scar tissue to be made in the lungs of asthmatic patients. This scar tissue is a major contributor during an asthma attack. It leads to a large reduction in the amount of air that can travel into the lungs and makes it hard for asthmatics to breath. Current treatments for asthma cannot prevent this scar tissue build up.
I made this discovery by growing human airway smooth muscle cells, a major cell type in the airway wall, from asthmatic and non asthmatic volunteers in dishes in the laboratory at the University of Sydney. In a world first, I showed that the asthmatic cells produced 20 times more of this scar creating protein. In the asthmatic cells I showed that the CTGF was able to cause more of the scar tissue proteins – collagen and fibronectin, to be made. To check that I had not changed the cells when I grew them in the laboratory I used a special microscope with a laser that enabled me to cut the airway smooth muscle cells out of a piece of fresh human lung. The gene which makes the scar creating protein was in the collected cells showing that this gene is in the human lung and contributes to the scar tissue build up.
I also found that asthmatics are less able to stop the action of this scar creating protein which adds to the scar formation. This is due to a lack of a molecule, present in the non asthmatics, that controls the production of the scar tissue.
My findings that CTGF production was increased in asthmatic cells, that it lead to a much greater release of scar tissue proteins and that the asthmatics lacked a control molecule to stop scar tissue formation are a major break through in asthma research. This research could be used to develop new drugs for the treatment of asthma which might stop asthmatics having trouble breathing.
Qualifications: BSc (Hons) University of Adelaide 1992, PhD University of New South Wales conferred Oct 1998 Department of Pharmacology, Bosch Building, D05 Department of Pharmacology, Bosch Building, D05