MicroRNA-30a Targets ATG5 and Attenuates Airway Fibrosis in Asthma by Suppressing Autophagy
MicroRNA-30a Targets ATG5 and Attenuates Airway Fibrosis in Asthma by Suppressing Autophagy
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DOI：
10.1007/s10753-019-01076-0
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发表时间：
2020-02-01
期刊：
影响因子：
5.1
通讯作者：
Pang, Fuzhen
中科院分区：
文献类型：
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作者：
Li, Bin Bin;Chen, Yun Long;Pang, Fuzhen
哮喘是儿童时期最常见的慢性疾病，慢性气道炎症；支气管组织纤维化是儿童哮喘常见的病理特征，新的数据表明自噬在气道炎症和纤维化介导的气道重塑中发挥着关键作用。本研究的目的是检查上皮 microRNA (miRNA) 的抗纤维化作用是否依赖于调节自噬介导的气道重塑，并确定相关因素和潜在机制。我们的结果显示，在哮喘儿童和卵清蛋白 (OVA) 小鼠模型中，miR-30a 下调，同时自噬相关蛋白上调；此外，我们观察到miR-30a通过下调自噬相关5（ATG5）来抑制自噬。然后，我们观察到miR-30a的过度表达抑制了支气管上皮细胞中白细胞介素33（IL-33）刺激的纤维形成和自噬流。体内实验表明，miR-30a 过表达可通过减少自噬来减少气道重塑。这项研究揭示了 miR-30a 在哮喘、IL-33 诱导的体外肺上皮细胞以及 OVA 诱导的体内气道炎症小鼠模型中先前未被认识的抗纤维化作用，并探讨了其潜在机制。
Asthma is the most common chronic disease of childhood, chronic airway inflammation; bronchial tissue fibrosis, is a pathological feature common to children asthma, and an emerging data has indicted that autophagy plays critical roles in airway inflammation and fibrosis-mediated airway remodeling. The aim of this study was to examine whether the antifibrotic effect of epithelial microRNAs (miRNAs) relies on regulating autophagy-mediated airway remodeling and to identify the factors involved and the underlying mechanisms. Our results showed miR-30a were downregulated in children with asthma and ovalbumin (OVA) mouse model in parallel with the upregulation of autophagy-related proteins; moreover, we observed miR-30a inhibited the autophagy by downregulated autophagy-related 5 (ATG5). Then, we observed that overexpression of miR-30a suppressed the fibrogenesis and autophagic flux which was stimulated by interleukin-33 (IL-33) in bronchial epithelial cells. In vivo experiments showed that miR-30a overexpression decreased airway remodeling by decreased autophagy. This study uncovered a previously unrecognized antifibrotic role of miR-30a in asthma, in IL-33-induced lung epithelial cells in vitro, and in a murine model of OVA-induced airway inflammation in vivo and explored the underlying mechanisms.