Role of gob-5 in mucus overproduction and airway hyperresponsiveness in asthma

Airway hyperresponsiveness (AHR), goblet cell metaplasia. and mucus overpro duction are important features of bronchial asthma, To elucidate the molecu lar mechanisms behind these pulmonary pathologies, we examined for genes pr eferentially expressed in the lungs of a murine model of allergic: asthma b y using suppression subtractive hybridization (SSH), We identified a gene c alled gob-5 that had a selective expression pattern in the airway epitheliu m with AHR, Here, we show that gob-5, a member of the calcium-activated chl oride channel family, is a key molecule in the induction of murine asthma, Intratracheal administration of adenovirus-expressing antisense gob-5 RNA i nto AHR-model mice efficiently suppressed the asthma phenotype, including A HR 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, int o the human mucoepidermoid cell line NCI-H292 induced mucus production as w ell as MUC5AC expression. Our results indicated that gob-5 may play a criti cal role in murine asthma, and its human counterpart hCLCA1 is therefore a potential target for asthma therapy.