转化生长因子β1对心肌细胞转化生长因子结合蛋白2表达的影响

Objective: To explore transforming growth factor beta 1 (TGF-β1) induced latent transforming growth factor binding protein 2 in neonatal rat cardiomyocytes with its underlying signal transduction pathway. Methods: Primary cultured cardiomyocytes were obtained from neonatal rats by enzymatic digestion method. LTBP2 gene and its protein expression were examined by Real-time PCR, Western blot analysis and immunocytochemistry. In order to further study the signal transduction pathway of TGF-β1，inhibitors of TGF-β1 signaling pathways were used to inhibit the effect of TGF-β1 and to observe the expression change of LTBP2. Results: The stimulation effect of TGF-β1 was dose-dependent, LTBP2 gene expression began to increase after 2 ng/ml ( P < 0.05) of stimulation, peaked at 5 ng/ml (P < 0.05) and reached a plateau after 10 ng/ml (P < 0.05), so we chose 5 ng/ml as the best stimulation dose of TGF-β1. The stimulation effect of TGF-β1 was also time-dependent, with the stimulation time extension, the expression of LTBP2 was increased, peaked at 12 h and declined at 24 h. Immunocytochemistry showed that TGF-β1 increased LTBP2 levels. Further signaling pathway study demonstrated that TGF-β1 induces expression of LTBP2 in cardiomyocytes via ERK pathway and PI3K pathway. Conclusions: TGF-β1 up-regulated LTBP2 expression in cardiomyocytes via ERK pathway and PI3K pathway.