Dual roles of chromatin remodeling protein BRG1 in angiotensin II-induced endothelial-mesenchymal transition
Endothelial-mesenchymal transition (EndMT) is considered one of the processes underlying tissue fibrosis by contributing to the pool of myofibroblasts. In the present study, we investigated the epigenetic mechanism whereby angiotensin II (Ang II) regulates EndMT to promote cardiac fibrosis focusing on the role of chromatin remodeling protein BRG1. BRG1 knockdown or inhibition attenuated Ang II-induced EndMT, as evidenced by down-regulation of CDH5, an endothelial marker, and up-regulation of COL1A2, a mesenchymal marker, in cultured vascular endothelial cells. On the one hand, BRG1 interacted with and was recruited by Sp1 to the SNAI2 (encoding SLUG) promoter to activate SNAI2 transcription in response to Ang II stimulation. Once activated, SLUG bound to the CDH5 promoter to repress CDH5 transcription. On the other hand, BRG1 interacted with and was recruited by SRF to the COL1A2 promoter to activate COL1A2 transcription. Mechanistically, BRG1 evicted histones from the target promoters to facilitate the bindings of Sp1 and SRF. Finally, endothelial conditional BRG1 knockout mice (CKO) exhibited a reduction in cardiac fibrosis, compared to the wild type (WT) littermates, in response to chronic Ang II infusion. In conclusion, our data demonstrate that BRG1 is a key transcriptional coordinator programming Ang II-induced EndMT to contribute to cardiac fibrosis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
|---|---|
| Enthalten in: |
Cell death & disease - 11(2020), 7 vom: 18. Juli, Seite 549 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Zilong [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 24.03.2021 Date Revised 18.07.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41419-020-02744-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM312597304 |
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| 100 | 1 | |a Li, Zilong |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Dual roles of chromatin remodeling protein BRG1 in angiotensin II-induced endothelial-mesenchymal transition |
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| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Endothelial-mesenchymal transition (EndMT) is considered one of the processes underlying tissue fibrosis by contributing to the pool of myofibroblasts. In the present study, we investigated the epigenetic mechanism whereby angiotensin II (Ang II) regulates EndMT to promote cardiac fibrosis focusing on the role of chromatin remodeling protein BRG1. BRG1 knockdown or inhibition attenuated Ang II-induced EndMT, as evidenced by down-regulation of CDH5, an endothelial marker, and up-regulation of COL1A2, a mesenchymal marker, in cultured vascular endothelial cells. On the one hand, BRG1 interacted with and was recruited by Sp1 to the SNAI2 (encoding SLUG) promoter to activate SNAI2 transcription in response to Ang II stimulation. Once activated, SLUG bound to the CDH5 promoter to repress CDH5 transcription. On the other hand, BRG1 interacted with and was recruited by SRF to the COL1A2 promoter to activate COL1A2 transcription. Mechanistically, BRG1 evicted histones from the target promoters to facilitate the bindings of Sp1 and SRF. Finally, endothelial conditional BRG1 knockout mice (CKO) exhibited a reduction in cardiac fibrosis, compared to the wild type (WT) littermates, in response to chronic Ang II infusion. In conclusion, our data demonstrate that BRG1 is a key transcriptional coordinator programming Ang II-induced EndMT to contribute to cardiac fibrosis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Kong, Xiaochen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yuanyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yangxi |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Liming |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Junli |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Yong |e verfasserin |4 aut | |
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