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Relationship between HSPA1A-regulated gene expression and alternative splicing in mouse cardiomyocytes and cardiac hypertrophy

BACKGROUND: Cardiac hypertrophy may be classified as either physiological or pathological. Pathological hypertrophy has a complex etiology and is genetically regulated. In this study, we used a mouse model of cardiac hypertrophy to explore the mechanisms of gene regulation, in particular, modulation...

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Autores principales: Li, Shuai, Yang, Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482330/
https://www.ncbi.nlm.nih.gov/pubmed/34659818
http://dx.doi.org/10.21037/jtd-21-1222
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author Li, Shuai
Yang, Ping
author_facet Li, Shuai
Yang, Ping
author_sort Li, Shuai
collection PubMed
description BACKGROUND: Cardiac hypertrophy may be classified as either physiological or pathological. Pathological hypertrophy has a complex etiology and is genetically regulated. In this study, we used a mouse model of cardiac hypertrophy to explore the mechanisms of gene regulation, in particular, modulation of the expression of target genes through transcription factor activity, regulation of immune and inflammation-associated genes and regulation of the alternative splicing of transcription factors. METHODS: Mouse models of pathological cardiac hypertrophy were established by transverse aortic constriction (TAC). We overexpressed HSPA1A in mouse cardiac HL-1 cells. GO and KEGG pathway annotation database was used to analyze all DEGs. RESULTS: The expression of HSPA1A differed significantly between TAC + dantrolene vs. sham + dantrolene (Sham was the non-TAC group, and DMSO was the contrast agent), and TAC + DMSO vs. sham + DMSO. The RNA-binding protein Zfp36 was found to be differentially expressed between both TAC + dantrolene vs. sham + dantrolene and TAC + DMSO vs. sham + DMSO. The expression of mki67 and gm5619 was significantly different between TAC + dantrolene and TAC + DMSO. HSPA1A was found to selectively regulate the expression of non-coding RNAs related to cardiac hypertrophy, including Rn7sk and RMRP. The downregulated genes were mainly related to inflammation and the immune response. HSPA1A negatively regulated alternative splicing of Asxl2 and positively regulated alternative splicing of Runx1. CONCLUSIONS: HSPA1A was closely related to cardiac hypertrophy. Zfp36 was also related to cardiac hypertrophy. Dantrolene may delay cardiac hypertrophy and ventricular remodeling by regulating the expression of the RNA-binding protein genes mki67 and gm5619. HSPA1A positively regulated the expression of the non-coding RNAs RN7SK and RMRP while negatively regulating the expression of inflammation- and immune response-related genes. HSPA1A can play a role in cardiac hypertrophy by regulating the alternative splicing of asxl2 and runx1.
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spelling pubmed-84823302021-10-14 Relationship between HSPA1A-regulated gene expression and alternative splicing in mouse cardiomyocytes and cardiac hypertrophy Li, Shuai Yang, Ping J Thorac Dis Original Article BACKGROUND: Cardiac hypertrophy may be classified as either physiological or pathological. Pathological hypertrophy has a complex etiology and is genetically regulated. In this study, we used a mouse model of cardiac hypertrophy to explore the mechanisms of gene regulation, in particular, modulation of the expression of target genes through transcription factor activity, regulation of immune and inflammation-associated genes and regulation of the alternative splicing of transcription factors. METHODS: Mouse models of pathological cardiac hypertrophy were established by transverse aortic constriction (TAC). We overexpressed HSPA1A in mouse cardiac HL-1 cells. GO and KEGG pathway annotation database was used to analyze all DEGs. RESULTS: The expression of HSPA1A differed significantly between TAC + dantrolene vs. sham + dantrolene (Sham was the non-TAC group, and DMSO was the contrast agent), and TAC + DMSO vs. sham + DMSO. The RNA-binding protein Zfp36 was found to be differentially expressed between both TAC + dantrolene vs. sham + dantrolene and TAC + DMSO vs. sham + DMSO. The expression of mki67 and gm5619 was significantly different between TAC + dantrolene and TAC + DMSO. HSPA1A was found to selectively regulate the expression of non-coding RNAs related to cardiac hypertrophy, including Rn7sk and RMRP. The downregulated genes were mainly related to inflammation and the immune response. HSPA1A negatively regulated alternative splicing of Asxl2 and positively regulated alternative splicing of Runx1. CONCLUSIONS: HSPA1A was closely related to cardiac hypertrophy. Zfp36 was also related to cardiac hypertrophy. Dantrolene may delay cardiac hypertrophy and ventricular remodeling by regulating the expression of the RNA-binding protein genes mki67 and gm5619. HSPA1A positively regulated the expression of the non-coding RNAs RN7SK and RMRP while negatively regulating the expression of inflammation- and immune response-related genes. HSPA1A can play a role in cardiac hypertrophy by regulating the alternative splicing of asxl2 and runx1. AME Publishing Company 2021-09 /pmc/articles/PMC8482330/ /pubmed/34659818 http://dx.doi.org/10.21037/jtd-21-1222 Text en 2021 Journal of Thoracic Disease. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Li, Shuai
Yang, Ping
Relationship between HSPA1A-regulated gene expression and alternative splicing in mouse cardiomyocytes and cardiac hypertrophy
title Relationship between HSPA1A-regulated gene expression and alternative splicing in mouse cardiomyocytes and cardiac hypertrophy
title_full Relationship between HSPA1A-regulated gene expression and alternative splicing in mouse cardiomyocytes and cardiac hypertrophy
title_fullStr Relationship between HSPA1A-regulated gene expression and alternative splicing in mouse cardiomyocytes and cardiac hypertrophy
title_full_unstemmed Relationship between HSPA1A-regulated gene expression and alternative splicing in mouse cardiomyocytes and cardiac hypertrophy
title_short Relationship between HSPA1A-regulated gene expression and alternative splicing in mouse cardiomyocytes and cardiac hypertrophy
title_sort relationship between hspa1a-regulated gene expression and alternative splicing in mouse cardiomyocytes and cardiac hypertrophy
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482330/
https://www.ncbi.nlm.nih.gov/pubmed/34659818
http://dx.doi.org/10.21037/jtd-21-1222
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