FLI-1 ameliorates cardiac hypertrophy by inhibiting IGF-1R/Gi/PLC pathway via up-regulation of Klotho

Abstract

Objective To investigate the effect of FLI-1 on Klotho-mediated IGF-1R/Gi/PLC pathway on cardiomyocyte hypertrophy. Methods The cells were divided into 8 groups: control group, model group, model+NC Vector group, model+pcDNA-FLI-1 group, model+NC Vector+NC siRNA group, model+NC Vector+Klotho siRNA group, model+pcDNA-FLI-1+NC siRNA group and model+pcDNA-FLI-1+Klotho siRNA group. Cardiomyocyte hypertrophy models were established by treating cells with isoproterenol (ISO), and the latter cells were transfected with pcDNA-FLI-1 and Klotho siRNA, respectively. Apoptosis was detected by flow cytometry; hypertrophic area was detected by phalloidin staining; apoptosis, hypertrophy and expression of IGF-1R/Gi/PLC pathway-related proteins were detected by Western blotting. Results Compared with the control group, the ISO group had increased apoptotic rate, cardiomyocyte surface area and IGF-1R, GNAI1 and PLCG1 expression, indicating successful modeling; compared with the model +NC Vector group, the model +pcDNA-FLI-1 group had decreased apoptosis, cardiomyocyte surface area and IGF-1R, GNAI1 and PLCG1 expression. Apoptosis, cardiomyocyte surface area, and IGF-1R, GNAI1 and PLCG1 expression were increased in the model +NC Vector+Klotho siRNA group compared with the model +NC Vector+NC siRNA group; apoptosis, cardiomyocyte surface area, and IGF-1R, GNAI1 and PLCG1 expression were decreased in the model +pcDNA-FLI-1+Klotho siRNA group compared with the model +pcDNA-FLI-1+NC siRNA group. Conclusion FLI-1 can inhibit IGF-1R/Gi/PLC pathway and reduce myocardial apoptosis and myocardial hypertrophy by up-regulating Klotho. [Key words] cardiomyocyte hypertrophy , FLI-1 , Klotho , IGF-1R/Gi/PLC pathway ,cell apoptosis ,

Keywords

• ardiomyocyte hypertrophy
• fli-1
• klotho
• igf-1r/gi/plc pathway
• cell apoptosis