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The role of ADAM33 in the pathogenesis of asthma

The role of ADAM33 in the pathogenesis of asthma
The role of ADAM33 in the pathogenesis of asthma
While asthma is a disorder of the conducting airways characterised by Th2-directed inflammation, a second set of mechanisms is being increasingly recognised as fundamental to disease chronicity and severity, for which the term "remodelling" has been used. The cellular and mediator responses underpinning airway remodelling involve aberrant communication between the airway epithelium and underlying mesenchyme, involving the generation of growth factors that lead to proliferation of fibroblasts and smooth muscle and the deposition of matrix proteins to cause airway wall thickening linked to bronchial hyperresponsiveness and fixed airflow obstruction. The identification of ADAM33 on chromosome 20p13 from positional cloning as a novel candidate gene involved in the pathogenesis of these structural and functional changes has opened the way to further insight into these processes that contribute to corticosteroid refractoriness. The preferential expression of ADAM33 in mesenchymal cells and its multiple molecular actions provide ample opportunity for incriminating this molecule in chronic asthma. Its association with progressive asthma and in predicting reduced lung function in young children suggest that ADAM33 has an important role in the natural history and possibly the origins of asthma, a disease unique to humans.
asthma, bronchial hyperresponsiveness, genetics, ADAM33, remodelling
0344-4325
361-375
Cakebread, Julie A.
f5aa15da-3462-4809-9e69-eef5d6d2df0d
Haitchi, H.-M.
68dadb29-305d-4236-884f-e9c93f4d78fe
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Powell, Robert M.
884d6594-3f50-4be5-9516-d64b29dad63d
Keith, Tim
e2072d11-7d5c-4f56-87f1-c73fda8f6c38
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Cakebread, Julie A.
f5aa15da-3462-4809-9e69-eef5d6d2df0d
Haitchi, H.-M.
68dadb29-305d-4236-884f-e9c93f4d78fe
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Powell, Robert M.
884d6594-3f50-4be5-9516-d64b29dad63d
Keith, Tim
e2072d11-7d5c-4f56-87f1-c73fda8f6c38
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc

Cakebread, Julie A., Haitchi, H.-M., Holloway, John W., Powell, Robert M., Keith, Tim, Davies, Donna E. and Holgate, Stephen T. (2004) The role of ADAM33 in the pathogenesis of asthma. Springer Seminars in Immunopathology, 25 (3-4), 361-375. (doi:10.1007/s00281-003-0153-z).

Record type: Article

Abstract

While asthma is a disorder of the conducting airways characterised by Th2-directed inflammation, a second set of mechanisms is being increasingly recognised as fundamental to disease chronicity and severity, for which the term "remodelling" has been used. The cellular and mediator responses underpinning airway remodelling involve aberrant communication between the airway epithelium and underlying mesenchyme, involving the generation of growth factors that lead to proliferation of fibroblasts and smooth muscle and the deposition of matrix proteins to cause airway wall thickening linked to bronchial hyperresponsiveness and fixed airflow obstruction. The identification of ADAM33 on chromosome 20p13 from positional cloning as a novel candidate gene involved in the pathogenesis of these structural and functional changes has opened the way to further insight into these processes that contribute to corticosteroid refractoriness. The preferential expression of ADAM33 in mesenchymal cells and its multiple molecular actions provide ample opportunity for incriminating this molecule in chronic asthma. Its association with progressive asthma and in predicting reduced lung function in young children suggest that ADAM33 has an important role in the natural history and possibly the origins of asthma, a disease unique to humans.

Full text not available from this repository.

More information

Published date: 2004
Keywords: asthma, bronchial hyperresponsiveness, genetics, ADAM33, remodelling

Identifiers

Local EPrints ID: 26976
URI: https://eprints.soton.ac.uk/id/eprint/26976
ISSN: 0344-4325
PURE UUID: a5e11c58-3294-464e-9ec7-87ff3ed35971
ORCID for H.-M. Haitchi: ORCID iD orcid.org/0000-0001-8603-302X
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464
ORCID for Donna E. Davies: ORCID iD orcid.org/0000-0002-5117-2991

Catalogue record

Date deposited: 25 Apr 2006
Last modified: 24 May 2019 00:39

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