In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 9 ( 2001-04-24), p. 5175-5180
Abstract:
Airway hyperresponsiveness (AHR), goblet cell metaplasia, and mucus
overproduction are important features of bronchial asthma. To elucidate the molecular mechanisms behind these pulmonary pathologies, we
examined for genes preferentially expressed in the lungs of a murine model of allergic asthma by using suppression subtractive hybridization
(SSH). We identified a gene called gob-5 that had a
selective expression pattern in the airway epithelium with AHR. Here, we show that gob-5 , a member of the calcium-activated
chloride channel family, is a key molecule in the induction of murine asthma. Intratracheal administration of adenovirus-expressing
antisense gob-5 RNA into AHR-model mice efficiently suppressed the asthma phenotype, including AHR and mucus
overproduction. In contrast, overexpression of gob-5 in
airway epithelia by using an adenoviral vector exacerbated the asthma phenotype. Introduction of either gob-5 or hCLCA1 , the human counterpart of gob-5 ,
into the human mucoepidermoid cell line NCI-H292 induced mucus production as well as MUC5AC expression. Our results
indicated that gob-5 may play a critical role in murine
asthma, and its human counterpart hCLCA1 is therefore a
potential target for asthma therapy.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.081510898
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2001
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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