报告题目：The biological function of mitogen activated protein kinase (MAPK) signalling in heart diseases
报告人：靳嘉巍，英国曼切斯特大学医学院心血管研究中心博士后
主持人：王平 教授
报告时间：9月12日 10:00-11:30（周四）
报告地点：闵行生科院534报告厅
报告人简介：靳嘉巍，1999年获得复旦大学医学院药物化学专业理学士学位，2004年获得复旦大学医学院肿瘤分子生物学专业硕士学位，2010年获得英国曼切斯特大学生命科学院药理学专业博士学位，之后在英国曼切斯特大学生命科学院、医学院心血管研究中心做博士后研究工作，主要从事心脏疾病分子生物学研究工作，包括MAPK 信号通路在心肌肥大、心衰和心律失常中的调控作用，也参与肥胖及相关代谢性疾病/肿瘤的分子生物学研究。
报告摘要：Cardiac hypertrophy and cardiac chronic arrhythmia are two common causes contributing to population morbidity and mortality with a prevalence increasing with age. Cardiac hypertrophy is characterised as a reactive increase in cardiac mass growth with a complex of ventricular remodelling. Atrial fibrillation (AF) is the most common form of sustained cardiac arrhythmia is associated with extensive atrial remodelling. An in-depth understanding of cardiac hypertrophy and atrial fibrillation and the capacity to regulate them has profound clinical implications.
The MAPK pathways provide an important connection between external stimuli and intracellular signals for cardiac response to stresses. Two important MAPK pathways: the MKK4-JNK and the ERK5 pathways have been implicated as important mediators of cardiac stress responses, but conflicting data have been yielded from previous studies due to that the results based entirely on in vitro cultured cardiomyocytes or transgenic and total knockout mice. Herein, the conditional mice with a cardiomyocyte-specific deletion of MKK4 or ERK5 were generated to dissect their in vivo roles and underlying signalling mechanisms in cardiac hypertrophy and atrial fibrillation.
Our results demonstrate for the first time that MKK4 acts a protective role against pathological but not physiological hypertrophy as well as against atrial arrhythmogenesis induced by TGF-β1-associated remodelling with age, suggesting the new potential of MKK4 as therapeutic target for treating hypertrophy and AF. ERK5 is essential for pathological hypertrophic remodelling and cardiomyocyte survival and its function in hypertrophic remodelling is mediated through regulation of MEF2C activity. These data significantly advances knowledge about biological functions of MAPK pathways in the heart.
