miR-142-3p is associated with aberrant WNT signaling during airway remodeling in asthma
miR-142-3p is associated with aberrant WNT signaling during airway remodeling in asthma
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miR-142- 3 p与哮喘气道重塑过程中WNT信号异常相关
DOI：
10.1152/ajplung.00113.2018
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发表时间：
2018-08-01
影响因子：
4.9
通讯作者：
Bellusci, Saverio
中科院分区：
文献类型：
--
作者：
Bartel, Sabine;Carraro, Gianni;Bellusci, Saverio
哮喘的特征是慢性炎症和呼吸道重塑。尽管炎症是可以控制的，但逆转重塑的治疗选择并不存在。因此，有一个巨大的和尚未得到满足的需要，以了解潜在的分子机制，以开发新的治疗方法。我们先前通过微调Wingless/整合酶I(WNT)信号，发现miR-142-3p在调节肺发育过程中的气道平滑肌(ASM)前体细胞增殖方面发挥关键作用。因此，我们在这里的目的是调查这种相互作用在哮喘中的相关性。我们对卵清蛋白诱导的过敏性呼吸道炎症的小鼠模型和哮喘患者的支气管活检组织及其分离的原代成纤维细胞进行了定量RT-PCR和免疫染色。在哮喘小鼠和人的肺高增殖区，miR-142-3p表达增加，而这种microRNA(MiRNA)在ASM细胞分化的区域被排除在外。MiR-142-3p的增加与其已知的靶标腺瘤性息肉病结肠的减少有关。此外，我们观察到miR-142-3p在早发或晚发重症哮喘患者的支气管活检组织中有不同的表达，这与WNT的不同特征相一致。我们的数据提示miR-142-3p可能通过控制WNT信号参与调节哮喘ASM细胞增殖和分化之间的平衡。因此，这种miRNA可能是预防哮喘ASM过度增殖的一个有趣的靶点。
Asthma is characterized by a chronic inflammation and remodeling of the airways. Although inflammation can be controlled, therapeutic options to revert remodeling do not exist. Thus, there is a large and unmet need to understand the underlying molecular mechanisms to develop novel therapies. We previously identified a pivotal role for miR-142-3p in regulating airway smooth muscle (ASM) precursor cell proliferation during lung development by fine-tuning the Wingless/Integrase I (WNT) signaling. Thus, we here aimed to investigate the relevance of this interaction in asthma. We performed quantitative RT-PCR and immune staining in a murine model for ovalbumin-induced allergic airway inflammation and in bronchial biopsies from patients with asthma and isolated primary fibroblasts thereof. miR-142-3p was increased in hyperproliferative regions of lung in murine and human asthma, whereas this microRNA (miRNA) was excluded from regions with differentiated ASM cells. Increases in miR-142-3p were associated with a decrease of its known target Adenomatous polyposis coli. Furthermore, we observed a differential expression of miR-142-3p in bronchial biopsies from patients with early or late onset severe asthma, which coincided with a differential WNT signature. Our data suggest that miR-142-3p is involved in regulating the balance between proliferation and differentiation of ASM cells in asthma, possibly via controlling WNT signaling. Thus, this miRNA might be an interesting target to prevent ASM hyperproliferation in asthma.