GSE158635
Hspa1a-regulated gene expression and alternative splicing in mouse cardiomyocytes are tightly related to cardiac hypertrophy
Regulatory factors play important roles in cardiac hypertrophy by regulating gene expression in cardiomyocytes.HSP70, a heat shock protein encoded by HSPA1A ,is induced by hypertrophic stimulation and then causes cardiac hypertrophy. However, the regulation mechanism of HSP70 in cardiac hypertrophy is unknown. In this study, we established the cardiac hypertrophy mouse model to explore the differentially expressed genes and found Hspa1a was significantly increased in treated samples. Then Hspa1a was overexpressed in mouse cardiac HL-1 cells and we analyzed the changes of transcriptome expression by high throughput sequencing. The results showed that HSPA1A selectively regulates the expression of ncRNAs (Rn7sk,Rmrp), negatively regulates the expression of genes involved in inflammatory and immune response, including Cxcl1,Ccl2,Ccl7,Cxcl5, Fas andC3, which were also validated by RT-qPCR experiment. The HSPA1A-regulated genes and ncRNAs are highly associated with cardiac hypertrophy. Alternative splicing analysis revealed HSPA1A preferred to regulate genes enriched in transcriptional regulation, including Asxl2 and Runx1. These results indicate that the heat shock protein-HSPA1A may play a role in the occurrence and development of myocardial hypertrophy by regulating the expression of immune inflammatory response related pathway genes and ncRNAs related to myocardial hypertrophy. Overall design: transcriptional analysis of HSPA1A overexpression and control in HL-1 cells