PMID- 29619372 OWN - NLM STAT- MEDLINE DCOM- 20180917 LR - 20181114 IS - 2314-6141 (Electronic) IS - 2314-6133 (Print) VI - 2018 DP - 2018 TI - Irradiated Human Umbilical Vein Endothelial Cells Undergo Endothelial-Mesenchymal Transition via the Snail/miR-199a-5p Axis to Promote the Differentiation of Fibroblasts into Myofibroblasts. PG - 4135806 LID - 10.1155/2018/4135806 [doi] LID - 4135806 AB - 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 alpha-smooth muscle actin (alpha-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. FAU - Yi, Minxiao AU - Yi M AUID- ORCID: 0000-0001-7957-2244 AD - Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China. FAU - Liu, Bo AU - Liu B AD - Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China. FAU - Tang, Yang AU - Tang Y AD - Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China. FAU - Li, Fang AU - Li F AD - Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China. FAU - Qin, Wan AU - Qin W AD - Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China. FAU - Yuan, Xianglin AU - Yuan X AUID- ORCID: 0000-0003-0201-3828 AD - Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China. LA - eng PT - Journal Article DEP - 20180212 PL - United States TA - Biomed Res Int JT - BioMed research international JID - 101600173 RN - 0 (Biomarkers) RN - 0 (MicroRNAs) RN - 0 (Snail Family Transcription Factors) RN - 0 (mirn199 microRNA, human) SB - IM MH - Biomarkers/metabolism MH - *Cell Differentiation MH - Coculture Techniques MH - Fibroblasts/*cytology/metabolism MH - Fibrosis MH - Gene Expression Regulation MH - Human Umbilical Vein Endothelial Cells/*metabolism/*radiation effects MH - Humans MH - Mesoderm/*metabolism MH - MicroRNAs/genetics/*metabolism MH - Myofibroblasts/*cytology/metabolism MH - Signal Transduction/genetics MH - Snail Family Transcription Factors/*metabolism MH - X-Rays PMC - PMC5830288 EDAT- 2018/04/06 06:00 MHDA- 2018/09/18 06:00 PMCR- 2018/02/12 CRDT- 2018/04/06 06:00 PHST- 2017/10/27 00:00 [received] PHST- 2018/01/09 00:00 [revised] PHST- 2018/01/17 00:00 [accepted] PHST- 2018/04/06 06:00 [entrez] PHST- 2018/04/06 06:00 [pubmed] PHST- 2018/09/18 06:00 [medline] PHST- 2018/02/12 00:00 [pmc-release] AID - 10.1155/2018/4135806 [doi] PST - epublish SO - Biomed Res Int. 2018 Feb 12;2018:4135806. doi: 10.1155/2018/4135806. eCollection 2018.