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Nicotinic Acid-Mediated Modulation of Metastasis-Associated Protein 1 Methylation and Inflammation in Brain Arteriovenous Malformation

We explored metastasis-associated protein 1 (MTA1) promoter methylation in the development of brain arteriovenous malformation (BAVM). The clinical data of 148 sex- and age-matched BAVMs and controls were collected, and the MTA1 DNA methylation in peripheral white blood cells (WBC) was assessed by b...

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Autores principales: Deng, Xinpeng, Zhou, Shengjun, Hu, Ziliang, Gong, Fanyong, Zhang, Junjun, Zhou, Chenhui, Lan, Wenting, Gao, Xiang, Huang, Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10605296/
https://www.ncbi.nlm.nih.gov/pubmed/37892177
http://dx.doi.org/10.3390/biom13101495
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author Deng, Xinpeng
Zhou, Shengjun
Hu, Ziliang
Gong, Fanyong
Zhang, Junjun
Zhou, Chenhui
Lan, Wenting
Gao, Xiang
Huang, Yi
author_facet Deng, Xinpeng
Zhou, Shengjun
Hu, Ziliang
Gong, Fanyong
Zhang, Junjun
Zhou, Chenhui
Lan, Wenting
Gao, Xiang
Huang, Yi
author_sort Deng, Xinpeng
collection PubMed
description We explored metastasis-associated protein 1 (MTA1) promoter methylation in the development of brain arteriovenous malformation (BAVM). The clinical data of 148 sex- and age-matched BAVMs and controls were collected, and the MTA1 DNA methylation in peripheral white blood cells (WBC) was assessed by bisulfite pyrosequencing. Among them, 18 pairs of case–control samples were used for WBC mRNA detection, 32 pairs were used for WBC MTA1 protein measurement, and 50 pairs were used for plasma inflammatory factor analysis. Lipopolysaccharide (LPS) treatment was used to induce an inflammatory injury cell model of human brain microvascular endothelial cells (BMECS). 5-Aza-2′-deoxycytidine (5-AZA), nicotinic acid (NA), and MTA1 siRNAs were used in functional experiments to examine BMECS behaviors. RT-qPCR, Western blot, and ELISA or cytometric bead arrays were used to measure the expression levels of MTA1, cytokines, and signaling pathway proteins in human blood or BMECS. The degree of MTA1 promoter methylation was reduced in BAVM compared with the control group and was inversely proportional to MTA1 expression. Plasma ApoA concentrations in BAVM patients were significantly lower than those in controls and correlated positively with MTA1 promoter methylation and negatively with MTA1 expression. The expression of cytokine was markedly higher in BAVM than in controls. Cell experiments showed that 5-AZA decreased the methylation level of MTA1 and increased the expression of MTA1 protein. LPS treatment significantly increased cytokine concentrations (p < 0.05). NA and MTA1 silencing could effectively reverse the LPS-mediated increase in IL-6 and TNF-α expression through the NF-κB pathway. Our study indicated that NA may regulate MTA1 expression by affecting promoter DNA methylation, improve vascular inflammation through the NF-κB pathway, and alleviate the pathological development of BAVM.
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spelling pubmed-106052962023-10-28 Nicotinic Acid-Mediated Modulation of Metastasis-Associated Protein 1 Methylation and Inflammation in Brain Arteriovenous Malformation Deng, Xinpeng Zhou, Shengjun Hu, Ziliang Gong, Fanyong Zhang, Junjun Zhou, Chenhui Lan, Wenting Gao, Xiang Huang, Yi Biomolecules Article We explored metastasis-associated protein 1 (MTA1) promoter methylation in the development of brain arteriovenous malformation (BAVM). The clinical data of 148 sex- and age-matched BAVMs and controls were collected, and the MTA1 DNA methylation in peripheral white blood cells (WBC) was assessed by bisulfite pyrosequencing. Among them, 18 pairs of case–control samples were used for WBC mRNA detection, 32 pairs were used for WBC MTA1 protein measurement, and 50 pairs were used for plasma inflammatory factor analysis. Lipopolysaccharide (LPS) treatment was used to induce an inflammatory injury cell model of human brain microvascular endothelial cells (BMECS). 5-Aza-2′-deoxycytidine (5-AZA), nicotinic acid (NA), and MTA1 siRNAs were used in functional experiments to examine BMECS behaviors. RT-qPCR, Western blot, and ELISA or cytometric bead arrays were used to measure the expression levels of MTA1, cytokines, and signaling pathway proteins in human blood or BMECS. The degree of MTA1 promoter methylation was reduced in BAVM compared with the control group and was inversely proportional to MTA1 expression. Plasma ApoA concentrations in BAVM patients were significantly lower than those in controls and correlated positively with MTA1 promoter methylation and negatively with MTA1 expression. The expression of cytokine was markedly higher in BAVM than in controls. Cell experiments showed that 5-AZA decreased the methylation level of MTA1 and increased the expression of MTA1 protein. LPS treatment significantly increased cytokine concentrations (p < 0.05). NA and MTA1 silencing could effectively reverse the LPS-mediated increase in IL-6 and TNF-α expression through the NF-κB pathway. Our study indicated that NA may regulate MTA1 expression by affecting promoter DNA methylation, improve vascular inflammation through the NF-κB pathway, and alleviate the pathological development of BAVM. MDPI 2023-10-08 /pmc/articles/PMC10605296/ /pubmed/37892177 http://dx.doi.org/10.3390/biom13101495 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Deng, Xinpeng
Zhou, Shengjun
Hu, Ziliang
Gong, Fanyong
Zhang, Junjun
Zhou, Chenhui
Lan, Wenting
Gao, Xiang
Huang, Yi
Nicotinic Acid-Mediated Modulation of Metastasis-Associated Protein 1 Methylation and Inflammation in Brain Arteriovenous Malformation
title Nicotinic Acid-Mediated Modulation of Metastasis-Associated Protein 1 Methylation and Inflammation in Brain Arteriovenous Malformation
title_full Nicotinic Acid-Mediated Modulation of Metastasis-Associated Protein 1 Methylation and Inflammation in Brain Arteriovenous Malformation
title_fullStr Nicotinic Acid-Mediated Modulation of Metastasis-Associated Protein 1 Methylation and Inflammation in Brain Arteriovenous Malformation
title_full_unstemmed Nicotinic Acid-Mediated Modulation of Metastasis-Associated Protein 1 Methylation and Inflammation in Brain Arteriovenous Malformation
title_short Nicotinic Acid-Mediated Modulation of Metastasis-Associated Protein 1 Methylation and Inflammation in Brain Arteriovenous Malformation
title_sort nicotinic acid-mediated modulation of metastasis-associated protein 1 methylation and inflammation in brain arteriovenous malformation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10605296/
https://www.ncbi.nlm.nih.gov/pubmed/37892177
http://dx.doi.org/10.3390/biom13101495
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