Study Of Cross-Talk Between Stat Family And Smads Pathway-Mediated Cardiomyocyte Hypertrophy In Cultured Neonatal Rat In Vitro

Objective:To study the signal transduction crosstalk between the stat family and smad pathway in cardiomyocyte of neonatal rat in vitro,and investigate the mechanism of cardiomyoctye hypertrophy.Methods:Cultured neonatal rat cardiomyocytes were used to evaluate the effects of Ang Ⅱand TGF-β1 on cardiomyoctye hypertrophy with or without their inhibitor valsartan and staurosporine,respectively.Protein content,beat frequency per minute,and cell surface area detection were used to evaluate the cardiomyocyte hypertrophy.The mRNA of Smad3 were measured by RT-PCR.Ratios of phospho-Stat1/total Stat1,phospho-Stat3/total Stat3 and Smad2/3 were detected by western blotting.Result:Protein content,beat frequency per minute,cell surface area were elevated in cardiomyocytes treated with Ang Ⅱ(10-7 mol/L)or TGF-β1(3 ng/ml)in a time-dependent manner compared with those control groups.The hallmark of cardiomyoctye hypertrophy such as Smad3 mRNA levels were elevated in the Ang Ⅱor TGF-β1 treated with groups compared to those without drug interfered with groups.The augmentation of ratios of phospho-Stat1/total Stat1,phospho-Stat3/total Stat3 and Smad2/3 in the two specific cells stimulated with Ang Ⅱor TGF-β1 were reversed by the selective AT1 receptor antagonist,Valsartan,and Staurosporine,a PKC inhibitor in a time-dependent manner.Conclusion:These findings indicate that the Ang Ⅱand TGF-β1 mediated the hypertrophy of cultured neonatal rat cardiomyocyte via the common Stat1,Stat3,and Smad2/3 signal pathway.The cross-talk between them in the cardiomyocyte may provide an effective means of ameliorating cardiomyoctye hypertrophy.