MicroRNA-200b deficiency is not sufficient to increase susceptibility to allergen-induced airway inflammation and dysfunction in mice.

Abstract

MicroRNA-200b (miR-200b) has emerged as a therapeutic option for reducing inflammation and airway dysfunction in asthma. miR-200b belongs to a family of miRNAs that regulate epithelial-to-mesenchymal (EMT) transition and IL-33 abundance. In asthma, miR-200b abundance is reduced in the airways and is correlated with disease severity. In addition, prophylactic treatment with a miR-200b mimetic reduces airway inflammation and airway dysfunction in a mouse model. However, it is unclear whether miR-200b deficiency is sufficient to drive airway dysfunction and airway inflammation in asthma. Here, we show that male and female mice deficient in miR-200b do not display heightened airway inflammation or alterations in lung function that are characteristic of asthma. Following sensitization with house dust mite (HDM), female miR-200b knockout (KO) mice have elevated total lung resistance and male miR-200b KO have increased airway resistance. However, neither male nor female miR-200b mice display any changes in methacholine sensitivity or responsiveness and do not have enhanced HDM-induced airway inflammation. Collectively, these findings suggest that loss of miR-200b does not drive airway inflammation and airway dysfunction in mice. Thus, although treatment with exogenous miR-200b may ameliorate inflammation in asthma, deficiency of miR-200b is not likely driving pathobiology in asthma.MicroRNA-200b regulates the abundance of key asthma-related genes. However, loss of miR-200b does not potentiate allergic asthma in a mouse model, suggesting that miR-200b deficiency may not be sufficient to drive of asthma pathogenesis.