心外膜源性细胞调控炎性反应促心脏再生机制研究

心外膜源性细胞(epicardium-derived cells, EPDCs)具有多分化潜能,参与新冠脉血管的构建和心脏组织的再生，调控心脏炎性微环境的稳态维持。我们前期工作发现c-Met是一个既可调控炎性微环境，又调控EPDCs的关键因子，研究c-Met参与诱导的心脏再生的炎性反应过程，有助于我们理解和干预心脏的炎性反应与损伤修复间的过程。本项目将使用具有天然心脏再生能力的斑马鱼模型以及哺乳动物模型，研究炎性激活c-Met+EPDCs在心脏再生中对于心肌重构的作用及分化谱系，阐明微环境c-Met+中性粒细胞、巨噬细胞等细胞亚型的潜在调控特征及对心脏再生治疗的利弊，揭示微环境中性粒细胞激活c-Met+EPDCs后诱导的心脏再生中的特异性信号通路，发现炎性调节因子激活EPDCs及心外膜EMT亚群选择性调控机制。最终建立促进心肌和血管生成的同时限制疤痕组织形成的再生治疗方法。

Epicardium derived cells (EPDCs) have the pluripotential of differentiation, participate in the construction of new coronary vessels and the regeneration of heart tissue, and regulate the homeostasis of cardiac inflammatory microenvironment. Our previous work found that c-Met is a key factor that can not only regulate the inflammatory microenvironment, but also regulate EPDCs. To study the inflammatory response process that c-Met participates in induced cardiac regeneration is helpful for us to understand and intervene the process between the inflammatory response and injury repair of the heart. Here we will use zebrafish model with natural heart regeneration ability and mammalian model to study inflammatory activation. The study focus on the effect of c-Met+ EPDCs on cardiac remodeling and differentiation lineage in cardiac regeneration, the potential regulatory characteristics of c-Met+ neutrophils, macrophages and other cell subtypes in microenvironment and heart regeneration, and the specific signaling pathway of c-Met+ EPDCs activation induced by microenvironmental neutrophils. Furthermore, we try to uncover specific inflammatory regulatory factors that stimulate EPDCs and epicardial EMT. The purpose of this project is to establish a regeneration therapy that promotes myocardial and vascular formation while limiting scar tissue formation.