Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
Biomed Res Int. 2018 Feb 12;2018:4135806. doi: 10.1155/2018/4135806. eCollection 2018.
Radiation induced pulmonary fibrosis (RIPF) is one of the major side effects of radiotherapy for lung cancer. Previous studies have shown that endothelial cells and activated myofibroblasts play a key role in RIPF. However, the interaction between irradiated endothelial cells and activation of myofibroblasts has not been reported. The aim of the present study was to examine whether irradiated endothelial cells would affect the differentiation of fibroblasts into myofibroblasts in the process of RIPF. In the current study, we used a coculture system that allowed direct contact between human fetal lung fibroblasts (MRC-5) and irradiated human umbilical vein endothelial cells (HUVECs). After 24 or 48 h, cells were sorted by flow cytometry. Radiation induced endothelial-mesenchymal transition (EndMT) by significantly increasing the expression of Snail and vimentin and reducing the expression of CD31 in HUVECs. In addition, irradiation of HUVECs induced the expression of collagen type I and -smooth muscle actin (-SMA) in MRC-5 cells. Further investigation indicated that irradiation of HUVECs induced the differentiation of fibroblasts into myofibroblasts through the Snail/miR-199a-5p axis. We conclude that irradiated endothelial cells undergo EndMT to promote differentiation of fibroblasts into myofibroblasts via the Snail/miR-199a-5p axis.
放射性肺纤维化（RIPF）是肺癌放疗的主要副作用之一。先前的研究表明内皮细胞和激活的肌成纤维细胞在 RIPF 中起关键作用。然而，辐照内皮细胞与肌成纤维细胞激活之间的相互作用尚未报道。本研究旨在探讨辐照内皮细胞是否会影响 RIPF 过程中纤维母细胞向肌成纤维细胞的分化。在本研究中，我们使用了一种共培养系统，允许人胎肺成纤维细胞（MRC-5）与人脐静脉内皮细胞（HUVEC）直接接触。24 或 48 小时后，通过流式细胞术对细胞进行分选。辐射通过显著增加 Snail 和波形蛋白的表达以及降低 HUVEC 中 CD31 的表达诱导内皮-间充质转化（EndMT）。此外，辐照 HUVEC 诱导 MRC-5 细胞中 I 型胶原和 -平滑肌肌动蛋白（-SMA）的表达。进一步的研究表明，辐照 HUVEC 通过 Snail/miR-199a-5p 轴诱导成纤维细胞向肌成纤维细胞分化。我们得出结论，辐照内皮细胞通过 Snail/miR-199a-5p 轴发生 EndMT，从而促进纤维母细胞向肌成纤维细胞分化。
