FGF20 Protecting Against Isoproterenol Induced Cardiomyocyte Hypertrophy by Inhibiting BMP4
MEI Lin1, WANG Xu2, CHEN Huinan2, ZHOU Xuan3*, CHEN Yunjie3*
FGF20 (fibroblast growth factor 20) has a protective role in cardiac hypertrophy, but its molecular mechanism still unclear. Therefore, this study is aimed to explore the molecular mechanisms of FGF20 protecting against cardiomyocyte hypertrophy. NRCMs (neonatal rat cardiomyocytes) were stimulated with 10 μmol/L ISO (isoproterenol) for 48 h to establish a cardiomyocyte hypertrophy model, and then co-treated with 100 ng/mL recombinant protein FGF20 or 50 ng/mL recombinant protein BMP4 (bone morphogenetic protein 4) for 48 h. Transcriptome was performed to identify DEGs (differential expression genes) between ISO group and ISO+FGF20 group. DEGs were subjected to GO, KEGG enrichment analysis and PPI (protein-protein interaction) network construction. Machine learning algorithms were employed to identify Core-DEGs (core differentially expressed genes), followed by ROC (receiver operating characteristic) analysis. Finally, the expression of Core-DEGs was validated by Western blot and RT-qPCR analysis, and TUNEL staining was employed to detect cardiomyocyte apoptosis. The result showed that FGF20 alleviated ISO-induced cardiomyocyte hypertrophy, evidenced by decreased levels of ANP and BNP proteins. Transcriptome analysis identified 42 DEGs after FGF20 treatment compared to ISO stimulation. GO and KEGG enrichment analyses revealed that 42 DEGs were associated with multiple immune regulation and apoptosis signaling pathways. Notably, Bmp4 was identified as the Core-DEG by two classic machine learning algorithms (LASSO and Random Forest) and its AUC value was 1. Furthermore, FGF20 inhibited BMP4 expression and cardiomyocyte apoptosis induced by ISO. However, activation of BMP4 counteracted the protection of FGF20 against myocardial hypertrophy, resulting in increased levels of ANP and BNP proteins and cardiomyocyte apoptosis.In summary, FGF20 exerts a protective effect on cardiomyocyte hypertrophy by suppressing apoptosis through the inhibition of BMP4.
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