制瘤素M（OSM）介导的心肌细胞去分化在糖尿病心肌病中的作用

Diabetic cardiomyopathy is characterized by cardiac myocardium pathological changes in the absence of coronary atherosclerosis. The risk of diabetic patients suffering from heart failure was significantly higher than non-diabetic individuals. Clarifying the new target for the treatment of diabetic cardiomyopathy is essential for reducing the cardiac mortality in diabetic patients. Cardiomyocyte dedifferentiation is an adaptive change stimulated by external factors. However, long-term and excessive cardiomyocyte dedifferentiation accelerates the progression of heart failure.Some studies have shown that OSM-mediated cardiomyocyte dedifferentiation plays a key role in cardiac remodeling and heart failure progression. Our previous study also demonstrated that OSM was up-regulated in the animal model of diabetic cardiomyopathy and associated with increased cardiomyocyte dedifferentiation. However, is OSM-mediated cardiomyocyte dedifferentiation essential in the development of diabetic cardiomyopathy? Whether OSM and its downstream signaling pathway is a new target for the treatment of diabetic cardiomyopathy is not well understood. Animal models of diabetic cardiomyopathy will be constructed in this project. The roles of OSM and its downstream MEK/ERK signaling pathway in the development of diabetic cardiomyopathy will be elucidated. This project will further help enrich the molecular mechanisms of diabetic cardiomyopathy and explore some new targets for the treatment of diabetic cardiomyopathy.

糖尿病心肌病是独立于冠状动脉病变的心肌病理改变，阐明糖尿病心肌病治疗的新靶点，对于降低糖尿病患者的心源性死亡率意义重大。心肌细胞去分化是心肌细胞受到外界刺激时发生的适应性改变，但长期、过度的心肌细胞去分化会加速心力衰竭的进展。研究表明，OSM介导的心肌细胞去分化在心脏重塑及心力衰竭的发生中起关键作用。我们的前期研究表明，糖尿病心肌病心肌组织中存在心肌细胞去分化，OSM表达上调。然而，OSM介导的心肌细胞去分化是否参与了糖尿病心肌病的发生发展？OSM及其下游信号通路是否能够成为糖尿病心肌病治疗的新靶点？目前尚不清楚。我们拟构建糖尿病心肌病动物模型，从整体、细胞、分子水平揭示OSM及其下游MEK/ERK信号通路介导的心肌细胞去分化在糖尿病心肌病发生发展中的分子机制。本项目将有助于进一步丰富糖尿病心肌病分子机制的理论基础，寻找逆转糖尿病心肌病的新靶点，为该疾病的防治提供新的思路。

糖尿病心肌病是独立于冠状动脉病变的心肌病理改变，阐明糖尿病心肌病治疗的新靶点，对于降低糖尿病患者的心源性死亡率意义重大。心肌细胞去分化是心肌细胞受到外界刺激时发生的适应性改变，但长期、过度的心肌细胞去分化会加速心力衰竭的进展。研究表明，OSM 介导的心肌细胞去分化在心脏重塑及心力衰竭的发生中起关键作用。我们的前期研究表明，糖尿病心肌病心肌组织中存在心肌细胞去分化，OSM 表达上调。然而，OSM 介导的心肌细胞去分化是否参与了糖尿病心肌病的发生发展？OSM 及其下游信号通路是否能够成为糖尿病心肌病治疗的新靶点？目前尚不清楚。我们拟构建糖尿病心肌病动物模型，从整体、细胞、分子水平揭示 OSM 及其下游 MEK/ERK 信号通路介导的心肌细胞去分化在糖尿病心肌病发生发展中的分子机制。本项目将有助于进一步丰富糖尿病心肌病分子机制的理论基础，寻找逆转糖尿病心肌病的新靶点，为该疾病的防治提供新的思路。