α7-integrin enhancing compounds regulate α7β1-integrin and laminin-α2 expression in airway smooth muscle cells via miRNA-mediated gene silencing mechanisms

Abstract

Asthma is characterized by airway inflammation, mucus production, and airway smooth muscle hyperreactivity that result in difficulty breathing. There has been an increasing need to develop new treatments for asthma that target airway smooth muscle in order to decrease airway remodeling. Previous studies have shown that ?7?1-integrin, a transmembrane protein receptor that promotes extracellular laminin-?2 binding, maintains a contractile airway smooth muscle phenotype and inhibits airway smooth muscle cell proliferation. However, the molecular mechanisms by which ?7-integrin regulates airway smooth muscle phenotype and function remain unknown. The hypothesis is that compounds targeting ?7-integrin expression regulate airway smooth muscle phenotype via miRNA-mediated gene silencing mechanisms. Our laboratory has verified that miR-124a binds to the 3’untranslated region of ?7-integrin and other studies have identified compounds modulating ?7-integrin expression in skeletal muscle. Non-asthmatic and asthmatic human airway smooth muscle cells were treated with these compounds and then transcript levels of ?7?1-integrin, laminin- ?2, and miR-124a were analyzed by quantitative real-time polymerase chain reaction. Results showed an inverse relationship between miR-124a and the expression of ?7?1- integrin and laminin-?2 in treated asthmatic differentiated cells.