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Trans-activation of eotaxin-1 by Brg1 contributes to liver regeneration

Infiltration of eosinophils is associated with and contributes to liver regeneration. Chemotaxis of eosinophils is orchestrated by the eotaxin family of chemoattractants. We report here that expression of eotaxin-1 (referred to as eotaxin hereafter), but not that of either eotaxin-2 or eotaxin-3, we...

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Autores principales: Fan, Zhiwen, Kong, Ming, Dong, Wenhui, Dong, Chunlong, Miao, Xiulian, Guo, Yan, Liu, Xingyu, Miao, Shuying, Li, Lin, Chen, Tingting, Qu, Yeqing, Yu, Fei, Duan, Yunfei, Lu, Yunjie, Zou, Xiaoping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9132924/
https://www.ncbi.nlm.nih.gov/pubmed/35614068
http://dx.doi.org/10.1038/s41419-022-04944-0
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author Fan, Zhiwen
Kong, Ming
Dong, Wenhui
Dong, Chunlong
Miao, Xiulian
Guo, Yan
Liu, Xingyu
Miao, Shuying
Li, Lin
Chen, Tingting
Qu, Yeqing
Yu, Fei
Duan, Yunfei
Lu, Yunjie
Zou, Xiaoping
author_facet Fan, Zhiwen
Kong, Ming
Dong, Wenhui
Dong, Chunlong
Miao, Xiulian
Guo, Yan
Liu, Xingyu
Miao, Shuying
Li, Lin
Chen, Tingting
Qu, Yeqing
Yu, Fei
Duan, Yunfei
Lu, Yunjie
Zou, Xiaoping
author_sort Fan, Zhiwen
collection PubMed
description Infiltration of eosinophils is associated with and contributes to liver regeneration. Chemotaxis of eosinophils is orchestrated by the eotaxin family of chemoattractants. We report here that expression of eotaxin-1 (referred to as eotaxin hereafter), but not that of either eotaxin-2 or eotaxin-3, were elevated, as measured by quantitative PCR and ELISA, in the proliferating murine livers compared to the quiescent livers. Similarly, exposure of primary murine hepatocytes to hepatocyte growth factor (HGF) stimulated eotaxin expression. Liver specific deletion of Brahma-related gene 1 (Brg1), a chromatin remodeling protein, attenuated eosinophil infiltration and down-regulated eotaxin expression in mice. Brg1 deficiency also blocked HGF-induced eotaxin expression in cultured hepatocytes. Further analysis revealed that Brg1 could directly bind to the proximal eotaxin promoter to activate its transcription. Mechanistically, Brg1 interacted with nuclear factor kappa B (NF-κB)/RelA to activate eotaxin transcription. NF-κB knockdown or pharmaceutical inhibition disrupted Brg1 recruitment to the eotaxin promoter and blocked eotaxin induction in hepatocytes. Adenoviral mediated over-expression of eotaxin overcame Brg1 deficiency caused delay in liver regeneration in mice. On the contrary, eotaxin depletion with RNAi or neutralizing antibodies retarded liver regeneration in mice. More important, Brg1 expression was detected to be correlated with eotaxin expression and eosinophil infiltration in human liver specimens. In conclusion, our data unveil a novel role of Brg1 as a regulator of eosinophil trafficking by activating eotaxin transcription.
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spelling pubmed-91329242022-05-27 Trans-activation of eotaxin-1 by Brg1 contributes to liver regeneration Fan, Zhiwen Kong, Ming Dong, Wenhui Dong, Chunlong Miao, Xiulian Guo, Yan Liu, Xingyu Miao, Shuying Li, Lin Chen, Tingting Qu, Yeqing Yu, Fei Duan, Yunfei Lu, Yunjie Zou, Xiaoping Cell Death Dis Article Infiltration of eosinophils is associated with and contributes to liver regeneration. Chemotaxis of eosinophils is orchestrated by the eotaxin family of chemoattractants. We report here that expression of eotaxin-1 (referred to as eotaxin hereafter), but not that of either eotaxin-2 or eotaxin-3, were elevated, as measured by quantitative PCR and ELISA, in the proliferating murine livers compared to the quiescent livers. Similarly, exposure of primary murine hepatocytes to hepatocyte growth factor (HGF) stimulated eotaxin expression. Liver specific deletion of Brahma-related gene 1 (Brg1), a chromatin remodeling protein, attenuated eosinophil infiltration and down-regulated eotaxin expression in mice. Brg1 deficiency also blocked HGF-induced eotaxin expression in cultured hepatocytes. Further analysis revealed that Brg1 could directly bind to the proximal eotaxin promoter to activate its transcription. Mechanistically, Brg1 interacted with nuclear factor kappa B (NF-κB)/RelA to activate eotaxin transcription. NF-κB knockdown or pharmaceutical inhibition disrupted Brg1 recruitment to the eotaxin promoter and blocked eotaxin induction in hepatocytes. Adenoviral mediated over-expression of eotaxin overcame Brg1 deficiency caused delay in liver regeneration in mice. On the contrary, eotaxin depletion with RNAi or neutralizing antibodies retarded liver regeneration in mice. More important, Brg1 expression was detected to be correlated with eotaxin expression and eosinophil infiltration in human liver specimens. In conclusion, our data unveil a novel role of Brg1 as a regulator of eosinophil trafficking by activating eotaxin transcription. Nature Publishing Group UK 2022-05-25 /pmc/articles/PMC9132924/ /pubmed/35614068 http://dx.doi.org/10.1038/s41419-022-04944-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Fan, Zhiwen
Kong, Ming
Dong, Wenhui
Dong, Chunlong
Miao, Xiulian
Guo, Yan
Liu, Xingyu
Miao, Shuying
Li, Lin
Chen, Tingting
Qu, Yeqing
Yu, Fei
Duan, Yunfei
Lu, Yunjie
Zou, Xiaoping
Trans-activation of eotaxin-1 by Brg1 contributes to liver regeneration
title Trans-activation of eotaxin-1 by Brg1 contributes to liver regeneration
title_full Trans-activation of eotaxin-1 by Brg1 contributes to liver regeneration
title_fullStr Trans-activation of eotaxin-1 by Brg1 contributes to liver regeneration
title_full_unstemmed Trans-activation of eotaxin-1 by Brg1 contributes to liver regeneration
title_short Trans-activation of eotaxin-1 by Brg1 contributes to liver regeneration
title_sort trans-activation of eotaxin-1 by brg1 contributes to liver regeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9132924/
https://www.ncbi.nlm.nih.gov/pubmed/35614068
http://dx.doi.org/10.1038/s41419-022-04944-0
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