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New study explains how asthma susceptibility gene causes breathing difficulties

Published: 28 April 2008

Researchers at the University of Southampton's School of Medicine have discovered how a gene, which is linked to susceptibility to asthma, contributes to the development or the progression of the disease. The findings of this new study may lead to novel treatments for asthma, as well as other diseases such as cancer and atherosclerosis or thickening of the arteries.

The asthma susceptibility gene ADAM33 was discovered in 2002 and is associated both with early life origins of asthma and with impaired lung function. However, its biological role and its contribution to the way asthma develops have not been understood until now.

The Southampton study, led by Professors Donna Davies and Stephen Holgate, describes the biological function of the gene for the first time, providing new insight into the progression and development of asthma.

ADAM33 protein is usually tethered in the cell membrane, but in asthma this tether is broken. Since ADAM33 is an enzyme, Professor Davies and her team reasoned that the untethered or 'rogue' enzyme could attack proteins it should not normally encounter.

They discovered that the cells lining the inner surface of blood vessels become a target for ADAM33, causing the formation of new blood vessels in a process called angiogenesis. These blood vessels can carry more inflammatory cells into the airways, causing swelling of the airways and changes in airway structure (termed 'remodelling'), resulting in breathing difficulties. The research team also identified a potential mechanism that would link environmental exposure to production of the rogue form of ADAM33.

Professor Davies explains: "Human asthma is triggered by both environmental and genetic factors. Our discovery that this rogue form of ADAM33 promotes angiogenesis suggests that it causes airways 'remodelling' to facilitate inflammation and reduced lung function. In both children and adults, the development of new blood vessels is believed to be an important aspect in the development of asthma, with increased levels linked to the severity of the disease. Treatments which specifically target the ADAM33 enzyme may therefore be effective in modifying the natural history of the disease.

"However, the importance of angiogenesis in many physiological and pathological processes broadens the range of the diseases in which the enzyme could be implicated, the most obvious being cancer and atherosclerosis or thickening of the arteries."

According to the charity Asthma UK 5.2m people in the UK are currently receiving treatment for asthma, including 1.1m children, and there is a person with asthma in one in five households in the UK.

The research paper, The soluble form of ADAM33 promotes angiogenesis: implications for airway remodelling in asthma, will be published in the June 2008 issue of the Journal of Allergy and Clinical Immunology and is available online now at www.jacionline.org/inpress

Professor Davies' and Holgate's research was funded by the Medical Research Council and several research charities.

Notes for editors

  • The soluble form of ADAM33 promotes angiogenesis: implications for airway remodelling in asthma will be published in the June issue of the Journal of Allergy and Clinical Immunology and is available online at www.jacionline.org/inpress

  • The research study was funded by The Medical Research Council UK, The Rayne Foundation, The British Lung Foundation, The Asthma Allergy and Inflammation Research Charity, the Roger Brooke Charitable Trust and the Wellcome Trust.

  • The University of Southampton is a leading UK teaching and research institution with a global reputation for leading-edge research and scholarship.

    This is one of the country's top institutions for engineering, computer science and medicine, and home to a range of world-leading research centres, including the National Oceanography Centre, Southampton, the Institute of Sound and Vibration Research, the Optoelectronics Research Centre, the Centre for the Developmental Origins of Health and Disease, and the Mountbatten Centre for International Studies.

    We combine academic excellence with an innovative and entrepreneurial approach to research, supporting a culture that engages and challenges students and staff in their pursuit of learning.

    As one of the UK's top 10 research universities, we offer first-rate opportunities and facilities for study and research across a wide range of subjects in humanities, health, science and engineering.

    We have over 22,000 students, around 5000 staff, and an annual turnover in the region of £325 million.

  • The Medical Research Council supports the best scientific research to improve human health. Its work ranges from molecular level science to public health medicine and has led to pioneering discoveries in our understanding of the human body and the diseases which affect us all.

  • For further information
    Sue Wilson, Communications, University of Southampton,
    Tel. 023 8059 5457, email: sjew@soton.ac.uk
    Hazel Lambert, MRC Press Officer,
    Tel. 020 7637 6011, email: hazel.lambert@headoffice.mrc.ac.uk

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