Increased expression of the human Ca2+-activated Cl- channel 1 (CaCC1) gene in the asthmatic airway.
Mucus overproduction is a clinical feature of asthma. Ca2+-activated Cl- channel 1 (CaCC1) has been identified as a protein that is expressed in intestinal epithelia and that plays an important role in fluid and electrolyte transport. Recently, its mouse counterpart, gob-5, was identified as a key molecule in the induction of murine asthma through mucus overproduction. To elucidate the relationship of CaCC1 to human asthma, we examined CaCC1 expression using real-time quantitative polymerase chain reaction analysis in bronchial tissues from patients with asthma and normal control subjects. The expression of CaCC1 was significantly upregulated in patients with bronchial asthma compared with control subjects. In situ hybridization and immunohistochemical analysis demonstrated that CaCC1 is located in the bronchial epithelium, especially in mucus-producing goblet cells. In vitro transfection of a CaCC1 expression vector into the human mucoepidermoid cell line, NCI-H292, increased mucus production and induced the MUC5AC gene. These results suggest that CaCC1 plays a direct role in mucus production and differentiation in goblet cells and may contribute to the pathogenesis of asthma through its mucus-inducing activity.
Hoshino
Makoto
M
Second Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan. hoshino@dn.catv.ne.jp
Morita
Shigeru
S
Iwashita
Hiroki
H
Sagiya
Yoji
Y
Nagi
Toshimi
T
Nakanishi
Atsushi
A
Ashida
Yasuko
Y
Nishimura
Osamu
O
Fujisawa
Yukio
Y
Fujino
Masahiko
M
D001249:Asthma / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D020397:Goblet Cells / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D055271:Mucin 5AC; D009077:Mucins; D009093:Mucus / Q000378:metabolism; D016133:Polymerase Chain Reaction; D020545:Respiratory Mucosa / Q000378:metabolism; D015854:Up-Regulation
D018118:Chloride Channels; C524678:MUC5AC protein, human; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D009077:Mucins; D002118:Calcium