Abstract:

BACKGROUND: Previous studies demonstrated that the early invention of neuregulin-1 (NRG-1) can induce embryonic stem cells (ESCs) to differentiate into cardiomyocytes.
OBJECTIVE: To further investigate the pathway of NRG-1 induces embryonic stem cells to differentiate into cardiomyocytes.
METHODS: The process of cardiomyocytes (CMs) differentiated from ESCs with or without NRG-1 treatment was observed continuously. RT-PCR was performed to detect the mRNA expression of early cardiac-restricted transcript factors Nkx2.5 and GATA-4 during differentiation. The protein expression of cardiac troponin T and phosphorylated protein kinase B was determined by immunhistochemistry (IHC), phosphorylated protein kinase B expression of CMs was analyzed by semiquantitative western blot analysis.
RESULTS AND CONCLUSION: The differentiation rate of CMs induced by NRG-1 was significantly higher than spontaneous CMs differentiation rate. NRG-1 exhibited a dose dependent up regulatory effect on the expression of GATA-4, Nkx2.5 mRNA, while NRG-1-induced increase of Nkx2.5 transcripts was inhibited by treatment with receptor antagonist and phosphatidylinositol 3-kinase (PI3K) inhibitor. Western blot analysis confirmed that the expression of phosphorylated protein kinase B of spontaneous beating CMs in embryoid body in NRG-1 induced group was relatively higher than that in spontaneous CMs differentiation group. The results suggested that NRG-1 promotes CMs differentiation of mouse ESCs via PI3K/phosphorylated protein kinase B/ phosphorylated protein kinase B activation.