Silencing of β1 integrin regulates airway remodeling by regulating the transcription of SOCE‑associated genes in asthmatic mice.

Abstract

The incidence of asthma is increasing globally; however, current treatments are only able to cure a certain proportion of patients. There is an urgent need to develop novel therapies. β1 integrin serves a role in the pathophysiology of asthma through the development of airway remodeling. The aim of the present study was to investigate silencing of the β1 integrin gene in pre-clinical models of allergic asthma. BALB/c mice were sensitized with ovalbumin through intraperitoneal injection and repeated aerosolized ovalbumin. A short hairpin RNA of the β1 integrin gene was designed and transfected into mouse models of asthma in vivo, in order to evaluate whether silencing of the β1 integrin gene affects airway smooth muscle cell proliferation and inflammation by regulating the mRNA expression of store-operated Ca2+ entry (SOCE)-associated genes. Silencing the β1 integrin gene may downregulate β1 integrin mRNA while not statistically decreasing α-smooth muscle actin gene expression and airway smooth muscle thickness. β1 integrin silencing was able to downregulate the transcription of SOCE-associated genes to normal levels, including calcium release-activated calcium modulator 1 and short transient receptor potential channel member 1, but not stromal interaction molecule 1, in asthma. Silencing of the β1 integrin gene additionally maintained nuclear factor of activated T-cells cytoplasmic 1 gene expression, and inflammatory cytokines interleukin-4 and interferon-γ at normal levels. The results of the present study provide evidence to suggest that silencing of the β1 integrin gene may be of therapeutic benefit for patients with asthma.