The transcription factor Friend leukemia integration-1 (FLI-1) is implicated in various cellular functions, including the regulation of cardiovascular function. This study aimed to elucidate the role and molecular mechanisms of FLI-1 in myocardial hypertrophy. We conducted FLI-1 overexpression interventions in ISO-induced H9C2 cells and mouse models of myocardial hypertrophy, subsequently assessing their effects on Klotho expression, cardiomyocyte hypertrophy, apoptosis, and IGF-1R/GNAI1PLCG1 signaling pathway activity. Our results demonstrated that ISO induction led to a time-dependent decrease in FLI-1 expression in H9C2 cells. Furthermore, FLI-1 overexpression enhanced Klotho expression in ISO-induced H9C2 cells and significantly inhibited ISO-induced cardiomyocyte hypertrophy and apoptosis. Furthermore, the overexpression of FLI-1 was found to attenuate the activity of the insulin-like growth factor type 1 receptor (IGF-1R)/GNAI1/PLCG1 signaling pathway in ISO-induced H9C2 cells. Notably, the silencing of Klotho negated the protective effects conferred by FLI-1 overexpression on cardiomyocyte hypertrophy and apoptosis, as well as its inhibitory impact on the IGF-1R/GNAI1/PLCG1 signaling pathway. In a murine model of myocardial hypertrophy, FLI-1 overexpression similarly exhibited a protective effect by mitigating myocardial hypertrophy and damage. These findings suggest that FLI-1 exerts a protective role in cardiac hypertrophy and apoptosis, potentially through the modulation of the Klotho and IGF-1R/GNAI1/PLCG1 pathways.
Tang et al. (Mon,) studied this question.