Journal article
miRNA‐200c‐3p promotes endothelial to mesenchymal transition and neointimal hyperplasia in artery bypass grafts
The Journal of pathology, Vol.253(2), pp.209-224
02/2021
DOI: 10.1002/path.5574
PMCID: PMC7839516
PMID: 33125708
Abstract
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.
Details
- Title: Subtitle
- miRNA‐200c‐3p promotes endothelial to mesenchymal transition and neointimal hyperplasia in artery bypass grafts
- Creators
- Dan Chen - The First Affiliated Hospital of Chongqing Medical UniversityCheng Zhang - The First Affiliated Hospital of Chongqing Medical UniversityJiangyong Chen - Barts and The London School of Medicine and Dentistry, Queen Mary University of LondonMei Yang - Boston UniversityTayyab A Afzal - University of Iowa, Internal MedicineWeiwei An - Barts and The London School of Medicine and Dentistry, Queen Mary University of LondonEithne M Maguire - Barts and The London School of Medicine and Dentistry, Queen Mary University of LondonShiping He - Barts and The London School of Medicine and Dentistry, Queen Mary University of LondonJun Luo - The First Affiliated Hospital of Chongqing Medical UniversityXiaowen Wang - The First Affiliated Hospital of Chongqing Medical UniversityYu Zhao - The First Affiliated Hospital of Chongqing Medical UniversityQingchen Wu - The First Affiliated Hospital of Chongqing Medical UniversityQingzhong Xiao - University of Iowa, Health, Sport, and Human Physiology
- Resource Type
- Journal article
- Publication Details
- The Journal of pathology, Vol.253(2), pp.209-224
- DOI
- 10.1002/path.5574
- PMID
- 33125708
- PMCID
- PMC7839516
- NLM abbreviation
- J Pathol
- ISSN
- 0022-3417
- eISSN
- 1096-9896
- Publisher
- John Wiley & Sons, Ltd
- Grant note
- 81700320 / ; CSTC2017jcyjAX0109 / Chongqing Science And Technology Bureau PG/15/11/31279; PG/15/86/31723; PG/16/1/31892 / ; 2019GDRC008 / Chongqing Municipal Health Commission
- Alternative title
- miRNA‐200c‐3p in EndoMT and neointima formation
- Language
- English
- Date published
- 02/2021
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984130695202771
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