BMAL1 regulates MUC1 overexpression in ovalbumin-induced asthma

Area of Science:

• * Respiratory Medicine
• * Chronobiology
• * Molecular Biology

Background:

• * Asthma symptoms exhibit daily rhythms, but the underlying molecular mechanisms are not fully understood.
• * Circadian rhythm genes are implicated in regulating inflammation and mucin production, key features of asthma.
• * Understanding the interplay between circadian rhythms and airway physiology is crucial for developing effective asthma treatments.

Purpose of the Study:

• * To investigate the role of the circadian rhythm gene BMAL1 in regulating mucin expression in asthma.
• * To explore the relationship between BMAL1 expression and mucin levels in both in vivo and in vitro asthma models.
• * To determine if targeting BMAL1 could be a potential therapeutic approach for asthma.

Main Methods:

• * Established ovalbumin (OVA)-induced asthma model in mice and used serum shock-treated human bronchial epidermal cells (16HBE).
• * Constructed a BMAL1 knockdown 16HBE cell line to assess the impact of BMAL1 on mucin expression.
• * Analyzed serum IgE, circadian gene expression, and mucin (MUC1, MUC5AC) levels in asthmatic mice and cells.

Main Results:

• * Asthmatic mice and cells showed rhythmic fluctuations in serum IgE and circadian genes, with increased MUC1 and MUC5AC expression.
• * MUC1 expression was negatively correlated with circadian rhythm genes, particularly BMAL1, in both models.
• * BMAL1 knockdown in 16HBE cells disrupted MUC1 rhythmic expression and led to its upregulation.

Conclusions:

• * The circadian rhythm gene BMAL1 plays a significant role in the periodic regulation of airway MUC1 expression in OVA-induced asthma.
• * BMAL1 influences MUC1 expression, suggesting a link between circadian disruption and airway hypersecretion in asthma.
• * Modulating BMAL1 activity to control periodic MUC1 changes presents a promising therapeutic avenue for asthma management.