Irradiation Activates MZF1 to Inhibit miR-541-5p Expression and Promote Epithelial-Mesenchymal Transition (EMT) in Radiation-Induced Pulmonary Fibrosis (RIPF) by Upregulating Slug.
Irradiation Activates MZF1 to Inhibit miR-541-5p Expression and Promote Epithelial-Mesenchymal Transition (EMT) in Radiation-Induced Pulmonary Fibrosis (RIPF) by Upregulating Slug.
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辐射激活 MZF1 通过上调 Slug 抑制 miR-541-5p 表达并促进辐射诱导肺纤维化 (RIPF) 中的上皮间质转化 (EMT)
DOI：
10.3390/ijms222111309
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发表时间：
2021-10-20
影响因子：
5.6
通讯作者：
Gu Y
中科院分区：
文献类型：
--
作者：
Liang X;Yan Z;Wang P;Liu Y;Ao X;Liu Z;Wang D;Liu X;Zhu M;Gao S;Xie D;Zhou P;Gu Y
了解miRNAs在上皮-间质转化（EMT）中的调控作用将有助于建立新的途径，进一步揭示辐射诱导的肺纤维化（RIPF）的机制，并确定预防和治疗靶点。在这里，我们证明了骨髓锌指1（MZF 1）对miR-541- 5 p的抑制促进了辐射诱导的EMT和RIPF。辐射可降低miR-541- 5 p在体外和体内的表达，并与RIPF的发展呈负相关。异位miR-541- 5 p表达在体外和体内抑制辐射诱导的EMT。Slug是miR-541- 5 p的功能靶点，其敲低可抑制辐射诱导的EMT。辐射后转录因子MZF 1的上调抑制了内源性miR-541- 5 p及其主要前体（pri-miR-541- 5 p）的表达，这调节了Slug对EMT过程的影响。我们的发现表明，异位miR-541- 5 p表达通过靶向Slug减轻小鼠中的RIPF。因此，辐射激活MZF 1以下调肺泡上皮细胞中的miR-541- 5 p，促进EMT并通过靶向Slug促进RIPF。我们的观察提供了对RIPF发展的进一步了解，并确定了潜在的预防和治疗靶点。
Understanding miRNAs regulatory roles in epithelial-mesenchymal transition (EMT) would help establish new avenues for further uncovering the mechanisms underlying radiation-induced pulmonary fibrosis (RIPF) and identifying preventative and therapeutic targets. Here, we demonstrated that miR-541-5p repression by Myeloid Zinc Finger 1 (MZF1) promotes radiation-induced EMT and RIPF. Irradiation could decrease miR-541-5p expression in vitro and in vivo and inversely correlated to RIPF development. Ectopic miR-541-5p expression suppressed radiation-induced-EMT in vitro and in vivo. Knockdown of Slug, the functional target of miR-541-5p, inhibited EMT induction by irradiation. The upregulation of transcription factor MZF1 upon irradiation inhibited the expression of endogenous miR-541-5p and its primary precursor (pri-miR-541-5p), which regulated the effect of the Slug on the EMT process. Our finding showed that ectopic miR-541-5p expression mitigated RIPF in mice by targeting Slug. Thus, irradiation activates MZF1 to downregulate miR-541-5p in alveolar epithelial cells, promoting EMT and contributing to RIPF by targeting Slug. Our observation provides further understanding of the development of RIPF and determines potential preventative and therapeutic targets.
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