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BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility
The transcription factor BTB and CNC homology 1(BACH1) has been linked to coronary artery disease risk by human genome-wide association studies, but little is known about the role of BACH1 in vascular smooth muscle cell (VSMC) phenotype switching and neointima formation following vascular injury. Th...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10201429/ https://www.ncbi.nlm.nih.gov/pubmed/36864760 http://dx.doi.org/10.1093/nar/gkad120 |
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author | Guo, Jieyu Qiu, Jingjing Jia, Mengping Li, Qinhan Wei, Xiangxiang Li, Liliang Pan, Qi Jin, Jiayu Ge, Fei Ma, Siyu He, Yunquan Lin, Jiayi Li, Yongbo Ma, Jinghua Jiang, Nan Zhi, Xiuling Jiang, Lindi Zhang, Jianyi Osto, Elena Jing, Qing Wang, Xinhong Meng, Dan |
author_facet | Guo, Jieyu Qiu, Jingjing Jia, Mengping Li, Qinhan Wei, Xiangxiang Li, Liliang Pan, Qi Jin, Jiayu Ge, Fei Ma, Siyu He, Yunquan Lin, Jiayi Li, Yongbo Ma, Jinghua Jiang, Nan Zhi, Xiuling Jiang, Lindi Zhang, Jianyi Osto, Elena Jing, Qing Wang, Xinhong Meng, Dan |
author_sort | Guo, Jieyu |
collection | PubMed |
description | The transcription factor BTB and CNC homology 1(BACH1) has been linked to coronary artery disease risk by human genome-wide association studies, but little is known about the role of BACH1 in vascular smooth muscle cell (VSMC) phenotype switching and neointima formation following vascular injury. Therefore, this study aims to explore the role of BACH1 in vascular remodeling and its underlying mechanisms. BACH1 was highly expressed in human atherosclerotic plaques and has high transcriptional factor activity in VSMCs of human atherosclerotic arteries. VSMC-specific loss of Bach1 in mice inhibited the transformation of VSMC from contractile to synthetic phenotype and VSMC proliferation and attenuated the neointimal hyperplasia induced by wire injury. Mechanistically, BACH1 suppressed chromatin accessibility at the promoters of VSMC marker genes via recruiting histone methyltransferase G9a and cofactor YAP and maintaining the H3K9me2 state, thereby repressing VSMC marker genes expression in human aortic smooth muscle cells (HASMCs). BACH1-induced repression of VSMC marker genes was abolished by the silencing of G9a or YAP. Thus, these findings demonstrate a crucial regulatory role of BACH1 in VSMC phenotypic transition and vascular homeostasis and shed light on potential future protective vascular disease intervention via manipulation of BACH1. |
format | Online Article Text |
id | pubmed-10201429 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-102014292023-05-23 BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility Guo, Jieyu Qiu, Jingjing Jia, Mengping Li, Qinhan Wei, Xiangxiang Li, Liliang Pan, Qi Jin, Jiayu Ge, Fei Ma, Siyu He, Yunquan Lin, Jiayi Li, Yongbo Ma, Jinghua Jiang, Nan Zhi, Xiuling Jiang, Lindi Zhang, Jianyi Osto, Elena Jing, Qing Wang, Xinhong Meng, Dan Nucleic Acids Res Gene regulation, Chromatin and Epigenetics The transcription factor BTB and CNC homology 1(BACH1) has been linked to coronary artery disease risk by human genome-wide association studies, but little is known about the role of BACH1 in vascular smooth muscle cell (VSMC) phenotype switching and neointima formation following vascular injury. Therefore, this study aims to explore the role of BACH1 in vascular remodeling and its underlying mechanisms. BACH1 was highly expressed in human atherosclerotic plaques and has high transcriptional factor activity in VSMCs of human atherosclerotic arteries. VSMC-specific loss of Bach1 in mice inhibited the transformation of VSMC from contractile to synthetic phenotype and VSMC proliferation and attenuated the neointimal hyperplasia induced by wire injury. Mechanistically, BACH1 suppressed chromatin accessibility at the promoters of VSMC marker genes via recruiting histone methyltransferase G9a and cofactor YAP and maintaining the H3K9me2 state, thereby repressing VSMC marker genes expression in human aortic smooth muscle cells (HASMCs). BACH1-induced repression of VSMC marker genes was abolished by the silencing of G9a or YAP. Thus, these findings demonstrate a crucial regulatory role of BACH1 in VSMC phenotypic transition and vascular homeostasis and shed light on potential future protective vascular disease intervention via manipulation of BACH1. Oxford University Press 2023-03-02 /pmc/articles/PMC10201429/ /pubmed/36864760 http://dx.doi.org/10.1093/nar/gkad120 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Gene regulation, Chromatin and Epigenetics Guo, Jieyu Qiu, Jingjing Jia, Mengping Li, Qinhan Wei, Xiangxiang Li, Liliang Pan, Qi Jin, Jiayu Ge, Fei Ma, Siyu He, Yunquan Lin, Jiayi Li, Yongbo Ma, Jinghua Jiang, Nan Zhi, Xiuling Jiang, Lindi Zhang, Jianyi Osto, Elena Jing, Qing Wang, Xinhong Meng, Dan BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility |
title | BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility |
title_full | BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility |
title_fullStr | BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility |
title_full_unstemmed | BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility |
title_short | BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility |
title_sort | bach1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility |
topic | Gene regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10201429/ https://www.ncbi.nlm.nih.gov/pubmed/36864760 http://dx.doi.org/10.1093/nar/gkad120 |
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