Dual roles of chromatin remodeling protein BRG1 in angiotensin II-induced endothelial-mesenchymal transition.

Cell Death & Disease
Zilong LiYong Xu

Abstract

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...Continue Reading

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Citations

Oct 6, 2020·Frontiers in Cell and Developmental Biology·Teng WuYong Xu
Apr 6, 2021·Frontiers in Cell and Developmental Biology·Wenhui DongYong Xu
Apr 27, 2021·Frontiers in Cell and Developmental Biology·Li LiuYong Xu
Jul 13, 2021·Frontiers in Cell and Developmental Biology·Baoyu ChenYong Xu
Aug 13, 2021·Frontiers in Cell and Developmental Biology·Yuyu YangYong Xu
Aug 27, 2021·Cellular Signalling·Alexis Paulina Jiménez-UribeJosé Pedraza-Chaverri
Oct 12, 2021·Frontiers in Cell and Developmental Biology·Baoyu ChenYifei Feng

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Methods Mentioned

BETA
transfections
transfection
electrophoresis
PCR
immunoprecipitation
ChIP
ChIP-seq
acetylation

Software Mentioned

SPSS
Image J

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