Radiation-induced pulmonary fibrosis (RIPF) is a major lung complication in using radiotherapy to treat thoracic diseases. MicroRNAs (miRNAs) are reported to be the therapeutic targets for many diseases. However, the miRNAs involved in the pathogenesis of RIPF are rarely studied as potential therapeutic targets. Alveolar epithelial cells participate in RIPF formation by undergoing epithelial-mesenchymal transition (EMT). Here we demonstrated the critical role of miR-155–5p in radiation-induced EMT and RIPF. Using the previously established EMT cell model, we found that miR-155–5p was significantly down-regulated through high-throughput sequencing. Irradiation could decrease the expression of miR-155–5p in intro and in vivo, and it was inversely correlated to RIPF formation. Ectopic miR-155–5p expression inhibited radiation-induced-EMT in vitro and in vivo. Knockdown of glycogen synthase kinase-3β (GSK-3β), the functional target of miR-155–5p, reversed the induction of EMT and enhanced the phosphorylation of p65, a subunit of NF-κB, which were mediated by the down-regulation of miR-155–5p. Moreover, our finding demonstrated that ectopic miR-155–5p expression alleviated RIPF in mice by the GSK-3β/NF-κB pathway. Thus, radiation downregulates miR-155–5p in alveolar epithelial cells that induces EMT, which contributes to RIPF using GSK-3β/NF-κB pathway. Our observation provides further understanding on the regulation of RIPF and identifies potential therapeutic targets.

放射致肺纤维化（RIPF）是使用放射疗法治疗胸腔疾病的主要肺部并发症。据报道，MicroRNA（miRNA）是许多疾病的治疗靶标。然而，很少研究与RIPF发病机理有关的miRNA作为潜在的治疗靶点。肺泡上皮细胞通过上皮-间质转化（EMT）参与RIPF的形成。在这里，我们证明了miR-155-5p在辐射诱导的EMT和RIPF中的关键作用。使用先前建立的EMT细胞模型，我们发现miR-155-5p通过高通量测序显着下调。照射能降低的miR-155-5p的表达在介绍和体内，它与RIPF的形成成反比。在体外和体内，异位miR-155-5p的表达均能抑制辐射诱导的EMT 。抑制糖原合酶激酶3β（GSK-3β）（miR-155-5p的功能靶标）可逆转EMT的诱导并增强NF-κB亚基p65的磷酸化，这是由下调介导的miR-155-5p。此外，我们的发现证明，异位miR-155-5p表达通过GSK-3β/NF-κB途径减轻了小鼠的RIPF。因此，辐射会下调诱导EMT的肺泡上皮细胞中的miR-155-5p，这会使用GSK-3β/NF-κB途径促成RIPF。我们的观察结果进一步了解了RIPF的调控，并确定了潜在的治疗靶点。