Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada.
Biology of Breathing Group, The Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada.
Am J Physiol Lung Cell Mol Physiol. 2023 Jul 1;325(1):L45-L53. doi: 10.1152/ajplung.00435.2022. Epub 2023 May 10.
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.
MicroRNA-200b (miR-200b) 已成为减少哮喘炎症和气道功能障碍的治疗选择。miR-200b 属于 miRNA 家族，可调节上皮间质转化和 IL-33 丰度。在哮喘中，miR-200b 在气道中的丰度降低，并与疾病严重程度相关。此外，预防性给予 miR-200b 模拟物可减少哮喘小鼠模型中的气道炎症和气道功能障碍。然而，miR-200b 缺乏是否足以驱动哮喘中的气道功能障碍和气道炎症尚不清楚。在这里，我们发现缺乏 miR-200b 的雄性和雌性小鼠不会出现气道炎症加剧或具有哮喘特征的肺功能改变。用屋尘螨 (HDM) 致敏后，雌性 miR-200b 敲除 (KO) 小鼠的总肺阻力升高，雄性 miR-200b KO 小鼠的气道阻力增加。然而，雄性和雌性 miR-200b 小鼠均未显示出乙酰甲胆碱敏感性或反应性的任何变化，也未增强 HDM 诱导的气道炎症。综上所述，这些发现表明 miR-200b 的缺失不会导致小鼠的气道炎症和气道功能障碍。因此，尽管外源性 miR-200b 的治疗可能改善哮喘中的炎症，但 miR-200b 的缺乏不太可能驱动哮喘的病理生物学。miR-200b 调节关键哮喘相关基因的丰度。然而，miR-200b 缺失在小鼠模型中不会增强过敏性哮喘，表明 miR-200b 缺乏可能不足以驱动哮喘发病机制。
