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Mechanistic study on the effect of cytokine-induced cardiogenesis in embryonic stem cells

Sau Kwan Law  Cecilia Sze-Lee Leung  Chi Lok Tse  Ka Long Yau  Christina Fung-Ping Leung  Suk Ying Tsang  
【摘要】:正Embryonic stem cells(ESCs) can self - renew and are pluripotent,meaning that they can proliferate indefinitely in culture while maintaining the ability to differentiate into all cell types,including the cardiomyocytes. During myocardial infarction,significant number of cardiomyocytes is lost.ESCs can be a potential source of cardiomyocytes for cell replacement therapy.During myocardial infarction,proinflammatory cytokines, including interleukin 1 -beta(IL-1 β ),interleukin 6(IL-6),interleukin 10(IL - 10) and interleukin 18(IL- 18) are released.The aims of the present study were to investigate the effects of these cytokines on the cardiac differentiation of ESCs,and the mechanisms underlying their effects on cardiac differentiation. The changes of intracellular reactive oxygen species(ROS) level upon cytokine treatment in differentiating embryoid bodies(EBs) were examined by confocal imaging.IL-1 β ,IL - 10 and IL - 18 were found to increase the intracellular ROS level in differentiating EBs.By western blotting,ROS were found to enhance cardiac differentiation by increasing the expression of cardiac transcription factors(TFs),consistent with previous studies.In addition,ROS was also found to post-translationally modify and activate the cardiac TFs. ROS was found to increase the expression of active phosphorylated TFs while decrease the expression of inactive phosphorylated TFs.The present results showed that some proinflammatory cytokines increased ROS generation in differentiating EBs while ROS increased cardiac differentiation by both increasing the expression and activity of cardiac TFs.Further studies would be required to investigate if these cytokines increase cardiac differentiation through increasing ROS.

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