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

• Atsushi Nakanishi

  Discovery Research Laboratories II, Pharmaceutical Discovery Research Division, and Pharmaceutical Research Division, Takeda Chemical Industries Ltd., 10 Wadai, Tsukuba, Ibaraki 300-4293, Japan

• Shigeru Morita

  Discovery Research Laboratories II, Pharmaceutical Discovery Research Division, and Pharmaceutical Research Division, Takeda Chemical Industries Ltd., 10 Wadai, Tsukuba, Ibaraki 300-4293, Japan

• Hiroki Iwashita

  Discovery Research Laboratories II, Pharmaceutical Discovery Research Division, and Pharmaceutical Research Division, Takeda Chemical Industries Ltd., 10 Wadai, Tsukuba, Ibaraki 300-4293, Japan

• Yoji Sagiya

  Discovery Research Laboratories II, Pharmaceutical Discovery Research Division, and Pharmaceutical Research Division, Takeda Chemical Industries Ltd., 10 Wadai, Tsukuba, Ibaraki 300-4293, Japan

• Yasuko Ashida

  Discovery Research Laboratories II, Pharmaceutical Discovery Research Division, and Pharmaceutical Research Division, Takeda Chemical Industries Ltd., 10 Wadai, Tsukuba, Ibaraki 300-4293, Japan

• Hideo Shirafuji

  Discovery Research Laboratories II, Pharmaceutical Discovery Research Division, and Pharmaceutical Research Division, Takeda Chemical Industries Ltd., 10 Wadai, Tsukuba, Ibaraki 300-4293, Japan

• Yukio Fujisawa

  Discovery Research Laboratories II, Pharmaceutical Discovery Research Division, and Pharmaceutical Research Division, Takeda Chemical Industries Ltd., 10 Wadai, Tsukuba, Ibaraki 300-4293, Japan

• Osamu Nishimura

  Discovery Research Laboratories II, Pharmaceutical Discovery Research Division, and Pharmaceutical Research Division, Takeda Chemical Industries Ltd., 10 Wadai, Tsukuba, Ibaraki 300-4293, Japan

• Masahiko Fujino

  Discovery Research Laboratories II, Pharmaceutical Discovery Research Division, and Pharmaceutical Research Division, Takeda Chemical Industries Ltd., 10 Wadai, Tsukuba, Ibaraki 300-4293, Japan

抄録

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.

収録刊行物

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 98 (9), 5175-5180, 2001-04-10

  Proceedings of the National Academy of Sciences

キーワード

• Multidisciplinary

詳細情報

• CRID: 1360574095951192576
• NII論文ID: 80012481590
• DOI: 10.1073/pnas.081510898
• ISSN: 10916490
• ISSN: 00278424
• ISSN: http://id.crossref.org/issn/07644450
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.081510898
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