Airway remodeling played a vital role in the development of asthma, and airway smooth muscle (ASM) mass was its hallmark. However, few strategies targeting ASM remodeling were developed in treating asthma. Nur77 was the transcription factor nuclear receptor involved in the pathogenesis of several lung diseases. Nur77 distribution and expression were determined in an HDM-mediated allergic asthma model. Its effect on airway hyperresponsiveness (AHR), chronic inflammation, and ASM remodeling in asthmatic mice was evaluated using a lentivirus-mediated shRNA. Possible mechanisms were explored by examining Nur77 actions and its underlying pathways in primary human AMC cells (ASMCs). In this study, we reported that Nur77 expression was mainly distributed along ASM and increased in lungs of HDM-challenged mice. Nur77 depletion by lentivirus-mediated shRNA ameliorated AHR, chronic inflammation, goblet cell hyperplasia, and airway remodeling in the asthmatic mouse model. By means of primary human ASMC, we discovered that Nur77 upregulation by HDM stimulation promoted cell proliferation and ROS production, as well as reduced antioxidant gene expression. These alterations might associate with MFN2/MAPK/AKT pathways. These findings broadened our understanding of airway remodeling and ASMC proliferation, which might provide a novel therapeutic target for asthma patients.

中文翻译：

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Nur77对室内尘螨诱发的哮喘患者气道重塑和ASMC增殖的调节作用

气道重塑在哮喘的发展中起着至关重要的作用，气道平滑肌（ASM）肿块是其标志。但是，在治疗哮喘方面，针对ASM重塑的策略很少。Nur77是参与多种肺部疾病发病机制的转录因子核受体。在HDM介导的过敏性哮喘模型中确定了Nur77的分布和表达。使用慢病毒介导的shRNA评估了其对哮喘小鼠气道高反应性（AHR），慢性炎症和ASM重塑的影响。通过检查Nur77的作用及其在原代人AMC细胞（ASMC）中的潜在途径，探索了可能的机制。在这项研究中，我们报道了Nur77表达主要沿ASM分布，并在受HDM攻击的小鼠的肺中增加。慢病毒介导的shRNA对Nur77的消耗可改善哮喘小鼠模型中的AHR，慢性炎症，杯状细胞增生和气道重塑。通过原代人ASMC，我们发现HDM刺激Nur77上调促进了细胞增殖和ROS产生，以及减少了抗氧化剂基因的表达。这些改变可能与MFN2 / MAPK / AKT途径有关。这些发现拓宽了我们对气道重塑和ASMC增殖的理解，这可能为哮喘患者提供新的治疗靶标。以及减少抗氧化剂基因的表达。这些改变可能与MFN2 / MAPK / AKT途径有关。这些发现拓宽了我们对气道重塑和ASMC增殖的理解，这可能为哮喘患者提供新的治疗靶标。以及抗氧化剂基因表达降低。这些改变可能与MFN2 / MAPK / AKT途径有关。这些发现拓宽了我们对气道重塑和ASMC增殖的理解，这可能为哮喘患者提供新的治疗靶标。