miRNA‐200c‐3p promotes endothelial to mesenchymal transition and neointimal hyperplasia in artery bypass grafts
| العنوان: | miRNA‐200c‐3p promotes endothelial to mesenchymal transition and neointimal hyperplasia in artery bypass grafts |
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| المؤلفون: | Weiwei An, Dan Chen, Shiping He, Xiao-Wen Wang, Mei Yang, Jiangyong Chen, Jun Luo, Eithne Margaret Maguire, Yu Zhao, Qingchen Wu, Cheng Zhang, Qingzhong Xiao, Tayyab Adeel Afzal |
| المصدر: | The Journal of Pathology |
| بيانات النشر: | John Wiley & Sons, Ltd, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Neointima, Male, Epithelial-Mesenchymal Transition, FERMT2, Pathology and Forensic Medicine, 03 medical and health sciences, Mice, 0302 clinical medicine, Serum response factor, Medicine, Animals, Humans, Neointimal hyperplasia, Gene knockdown, Original Paper, Hyperplasia, biology, microRNA, business.industry, Mesenchymal stem cell, post‐angioplasty restenosis, Endothelial Cells, Membrane Proteins, arterial bypass graft, neointima, medicine.disease, Original Papers, Neoplasm Proteins, Up-Regulation, Endothelial stem cell, Mice, Inbred C57BL, MicroRNAs, 030104 developmental biology, medicine.anatomical_structure, miRNA‐200c‐3p, 030220 oncology & carcinogenesis, Cancer research, biology.protein, endothelial cell, Female, Vascular Grafting, atherosclerosis, business, endothelial to mesenchymal transition, Artery |
| الوصف: | Increasing evidence has suggested a critical role for endothelial‐to‐mesenchymal transition (EndoMT) in a variety of pathological conditions. MicroRNA‐200c‐3p (miR‐200c‐3p) has been implicated in epithelial‐to‐mesenchymal transition. However, the functional role of miR‐200c‐3p in EndoMT and neointimal hyperplasia in artery bypass grafts remains largely unknown. Here we demonstrated a critical role for miR‐200c‐3p in EndoMT. Proteomics and luciferase activity assays revealed that fermitin family member 2 (FERM2) is the functional target of miR‐200c‐3p during EndoMT. FERMT2 gene inactivation recapitulates the effect of miR‐200c‐3p overexpression on EndoMT, and the inhibitory effect of miR‐200c‐3p inhibition on EndoMT was reversed by FERMT2 knockdown. Further mechanistic studies revealed that FERM2 suppresses smooth muscle gene expression by preventing serum response factor nuclear translocation and preventing endothelial mRNA decay by interacting with Y‐box binding protein 1. In a model of aortic grafting using endothelial lineage tracing, we observed that miR‐200c‐3p expression was dramatically up‐regulated, and that EndoMT contributed to neointimal hyperplasia in grafted arteries. MiR‐200c‐3p inhibition in grafted arteries significantly up‐regulated FERM2 gene expression, thereby preventing EndoMT and reducing neointimal formation. Importantly, we found a high level of EndoMT in human femoral arteries with atherosclerotic lesions, and that miR‐200c‐3p expression was significantly increased, while FERMT2 expression levels were dramatically decreased in diseased human arteries. Collectively, we have documented an unexpected role for miR‐200c‐3p in EndoMT and neointimal hyperplasia in grafted arteries. Our findings offer a novel therapeutic opportunity for treating vascular diseases by specifically targeting the miR‐200c‐3p/FERM2 regulatory axis. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland. |
| اللغة: | English |
| تدمد: | 1096-9896 0022-3417 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::27a5b56e1fe0428a900e93de6ce32415Test http://europepmc.org/articles/PMC7839516Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....27a5b56e1fe0428a900e93de6ce32415 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10969896 00223417 |
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