Methacholine Could Induce Asthma-Like Changes at the Molecular Level

Abstract

Background: The typical symptoms of asthma, including airway hyperresponsiveness (AHR) and airway remodeling, induce mechanical stress. Despite its crucial role in tissue development and pathophysiology, the role of mechanical stress in the development of asthma and its impact on the induction of AHR remain unclear. In this study, we aimed to investigate the potential contribution of mechanical stress to asthma by using a mouse model. Methods: Healthy mice were challenged with methacholine (METH) and compared with an allergic airway inflammation model induced by ovalbumin (OVA). Different approaches, including immunofluorescence, immunohistochemical staining, Western blot analysis, and histopathology were employed to detect pathological changes in the lung tissue of the experimental mice. Transcriptome analysis was conducted to identify the genetic changes in AHR-related genes within the lung tissue of mice following METH treatment. Results: METH treatment did not promote allergic phenotypes, but induced asthma-like changes in gene expression profiles. Affected genes were enriched in the immune response and inflammation-related genes, including genes involved in granulocyte migration and inflammatory reactions. Importantly, mechanical force perception ability was significantly enhanced in the OVA-induced allergic airway inflammation mouse lung, evidenced by increased expression of mechanoreceptor proteins. Conclusions: Short-term bronchial constriction without inflammation may not lead to tissue remodeling. However, genes involved in asthma development remain active.