To demonstrate the value of this system, we targeted <i>SPDEF</i>, which encodes a transcription factor previously shown to be essential for the differentiation of MUC5AC-producing goblet cells in mouse models of asthma.
Airway mucus hypersecretion is one of the most serious pathophysiological symptoms of chronic airway inflammatory diseases, and the human mucin 5AC (MUC5AC) gene has been reported to be a major component of respiratory secretions related to asthma and chronic obstructive pulmonary disease.
Mucins are glycoproteins that are mainly responsible for the viscoelastic property of mucus, and MUC5AC is a major mucin glycoprotein that is overproduced in asthma.
The rs11603634 G allele was associated with increased expression of MUC5AC mRNA in bronchial epithelial brush samples via proxy SNP rs11602802; (p=2·50 × 10<sup>-5</sup>) and MUC5AC mRNA was increased in bronchial epithelial samples from patients with severe asthma (in two independent analyses, p=0·039 and p=0·022).
Decreased stat6 increased transcription factor FOXA2, and the relatively increased FOXA2 further decreased the level of Muc5ac and mucous hypersecretion in OVA-induced asthma.
In light of the current standard therapies' limited and inadequate direct effect on airway mucus hypersecretion, our study showing AEC-PPARγ's role as a transcriptional repressor of MUC5AC highlights this receptor's potential as a pharmacological target for asthma.
Sputum MUC5AC concentrations were 7.6 μg/mL in control subjects, 22.4 μg/mL in those with stable asthma (P = .17), and 44.7 μg/mL in those with acute asthma (P < .05).
Our results showed that Muc5ac and IL-1β were up-regulated in 41 patients with asthma and that Muc5ac overexpression was related with IL-1β in asthma (R<sup>2</sup>=0.668, p≪0.001).
Mice lacking functional NADPH oxidases due to knockout of p47 and mice with epithelial-targeted transgenic expression of a CaMKII inhibitory peptide or wild-type mice treated with inhaled KN-93, an experimental small-molecule CaMKII antagonist, were protected against increases in ICl, MUC5AC expression, and airway hyperreactivity to inhaled methacholine.
These results suggested that SO(2) could increase the expressions of MUC5AC and ICAM-1 on the transcription and translation levels in the lungs and tracheas from asthmatic rats, which might be one of the possible mechanisms that SO(2) pollution aggravates asthma disease.
With in situ hybridization, a stronger expression of CaCC1 mRNA was further detected throughout the bronchial tissues from patients with asthma than control subjects (P<0.01); Samples from asthmatics were showed a stronger staining for MUC5AC than those in control subjects (P<0.05); AB-PAS staining revealed more mucins and goblet cells in asthmatic bronchial epithelium and submucosal gland comparing to that in control subjects (P<0.05).
MUC5AC was the predominant mucin gene expressed in healthy subjects and subjects with asthma, and MUC5AC protein was increased in the subjects with asthma.
There was a significant positive correlation between EGFR immunoreactivity and the area of MUC5AC-positive staining in both asthmatics and healthy subjects.