CCNY调控Wnt/β-catenin信号通路介导心梗后心肌再生机制的研究

促进原位心肌细胞增殖再生以代替丢失心肌细胞为目标的再生医学一直以来都是医学界研究热点。新生小鼠心尖切除后能够完全再生，但是这种再生能力在出生后7天丢失。我们前期研究曾报道PDGFRβ-CDKN2A信号通路能够促进心肌再生；近期研究发现，细胞周期蛋白CCNY能够被CDKN2A调控，AAV9过表达CCNY能促进心肌细胞增殖再生，同时激活Wnt/β-catenin通路。提示CCNY可能在心肌细胞增殖再生中扮演重要角色。本研究计划：1、构建心肌细胞特异性敲除Ccny小鼠1天龄心梗模型，分析CCNY在心肌再生中作用。2、繁殖Cdkn2a和Ccny双敲小鼠，构建心梗模型，证明CDKN2A调控CCNY表达在心肌再生过程中的作用。3、分离原代心肌细胞体外行干预实验，旨在探讨CCNY调控Wnt/β-catenin通路心肌增殖再生的具体机制。本研究将进一步完善心肌再生的细胞分子机制，为心肌再生提供新靶点。

Regenerative medicine, which promotes the regeneration of in situ cardiomyocytes to replace the lost cardiomyocytes, has always been a research hotspot in the medical field. Cardiomyocytes of newborn mice can be completely regenerated after apical resection, but this ability to regenerate lost 7 days after birth. Our previous studies have reported that PDGFRβ-CDKN2A signaling pathway can promote heart regeneration. Recently, we found that CCNY can be regulated by CDKN2A. Overexpression of CCNY by administrating AAV9 can promote the proliferation and regeneration of cardiomyocytes, and activate Wnt/β-catenin pathway. These results suggest that CCNY may play an important role in the process of cardiomyocyte proliferation and heart regeneration. This topic will be: 1. Establish a 1-day-old myocardial infarction model in cardiomyocyte specific knockout CCNY mice to analyze the role of CCNY in myocardial regeneration; 2. Breed Cdkn2a knockout and Ccny specific knockout mice, and construct myocardial injury model to prove the role of CDKN2A regulating CCNY expression in the process of myocardial regeneration; 3.In vitro treating isolated primary cardiomyocytes to investigate the mechanism of CCNY in regulating Wnt/β - catenin signaling pathway in cardiomyocyte proliferation and heart regeneration. This study will further improve the cellular and molecular mechanism of myocardial regeneration and provide new targets for myocardial regeneration.