Wnt/β-catenin信号通路在心梗后心肌损伤和重构中起到重要作用，R-spondin1(RSPO1)通过与其受体LGR4结合介导Wnt/β-catenin信号通路激活。前期研究表明: 1)血清RSPO1在心梗后心衰患者显著升高，且与左室射血分数呈负相关；2)小鼠心梗后血清和心脏中RSPO1显著增高，中和RSPO1显著改善心梗后心功能和β-catenin激活；3)敲除LGR4显著改善小鼠心梗后心脏重构和心功能，提示心肌缺血损伤后表达和释放的RSPO1可能通过与其受体LGR4结合，促进Wnt/β-catenin通路激活，加重心梗后心肌损伤和重构。因此，本课题将继续探讨: 1)RSPO1/LGR4/β-catenin通路在心梗后心肌损伤和重构的功能作用及其分子机制；2)RSPO1的表达调控机制；3)从临床方面研究血清RSPO1与心梗后心衰预后的相关性。为心梗后心衰防治提供新思路。

Wnt/β-catenin signaling pathway plays an important role in myocardial injury and remodeling after myocardial infarction. R-spondin1 (RSPO1) activates the Wnt/β-catenin signaling pathway by binding to its receptor LGR4. Our previous studies have showed that: 1) Serum levels of RSPO1 were significantly increased in patients with heart failure after myocardial infarction, and negatively correlated with left ventricular ejection fraction; 2) RSPO1 was significantly increased in serum and heart after MI in mice, and neutralization of RSPO1 significantly improved cardiac function and decreased β-catenin activation after myocardial infarction; 3) Defeciency of LGR4 significantly improves cardiac remodeling and dysfunction after myocardial infarction. These above results suggested that ischemia induced the expression and release of RSPO1, which may contribute to post MI injury and left ventricular remodeling via binding to LGR4, and activation of wnt/β-catenin pathway. Therefore, based on this hypothesis, the present project will continue to investigate : 1) the functional role and mechanistic insights of RSPO1/LGR4/β-catenin pathway in myocardial injury and remodeling after myocardial infarction; 2) the regulatory mechanism of RSPO1 expression; 3) the prognostic significance of serum RSPO1 in patients with heart failure after myocardial infarction. These results may pave the way for prevention and treatment of heart failure.