Fam117b Regulating cAMP Signaling Pathway to Promote Pathological Myocardial Hypertrophy
Objective:Mouse heart transcriptome sequencing data were analyzed by weighted gene coexpression network analysis (WGCNA) to screen genes and cell signaling pathways related to the occurrence with myocardial hypertrophy. Methods:A mouse model of myocardial hypertrophy was constructed by transverse aortic constriction(TAC) and evaluated at the in vitro,anatomical and pathological levels. Transcriptome sequencing was performed on mouse myocardial tissue to screen the genes with different expression.Gene set enrichment analysis(GSEA) and WGCNA were used to screen proteins and cell signaling pathways associated with myocardial hypertrophy.Results:Four weeks after the establishment of the model,the structure and function of the mouse heart were significantly changed,mainly in the end diastolic thickness(LVPWd) of the left ventricular posterior wall significantly increased compared with that of the control mice(P<0.05),while the left ventricular ejection fraction(LVEF) and left ventricular short axis shortening rate(LVFS) significantly decreased compared with that of the control group(P<0.05).The heart-to-body ratio in model group and tibia ratio in control group significantly increased(P<0.05).The results of wheat germ lectin/agglutinin(WGA) staining showed that the area of myocardial cells in the model group was significantly increased compared with that in the control group(P<0.05).Transcriptome sequencing of mouse myocardial tissue showed that 451 and 225 genes were significantly up-regulated or down-regulated in the myocardial tissue of the model group compared with that of the control group.By GSEA analysis of differential genes,cyclic adenosine phosphate(cAMP) signaling pathway obviously enriched,and it was significantly upregulated in myocardial tissue of model group mice. The results of WGCNA analysis of mouse myocardial transcriptome sequencing data showed that the co-expression network composed of 385 genes associated with the phenotype of myocardial hypertrophy,including 19 significantly up-regulated genes and 32 significantly down-regulated genes.Through gene ontology(GO) analysis of co-expression network,multiple biological processes closely related to myocardial hypertrophy were obtained,such as protein metabolism and phosphorylation,organ development,cell apoptosis,etc.Further correlation analysis showed that the expression of the gene Fam117b in the co-expression network was positively correlated with the gene expression in the cAMP signaling pathway in the heart of mice with myocardial hypertrophy,and its expression was significantly up-regulated in the myocardial tissue of mice in the model group. Conclusion:Fam117b can induce pathological myocardial hypertrophy by activating cAMP signaling pathway,which will provide a new target for clinical treatment of this disease.
pathological myocardial hypertrophycyclic adenosine phosphateFam117btranscriptomeweighted gene coexpression network analysisexperimental study
万方数据
维普
