心房颤动（AF）最终导致心房纤维化，而心房纤维化又可促进AF的维持，形成恶性循环。目前针对心房纤维化尚无有效防治。文献及我们的研究发现：盐皮质激素受体（MR）可作为心房纤维化的重要调控靶点，并可能特异性地通过心房成纤维细胞发挥作用，但其具体机制尚不完全明确。因此提出假说：心房成纤维细胞MR可能是特异性调控心房纤维化的关键靶点，并可能通过其下游AngII/TGF-β相关信号通路以及细胞间相互作用调控心房纤维化。本研究将应用自主创新成纤维细胞特异性MR敲除或过表达的心房特异性纤维化小鼠，通过细胞分子生物学和电生理学手段，研究成纤维细胞 MR对心房纤维化的影响，并针对其机制研究MR对AngII/AT1R 和 TGF-β/SMAD通路激活与炎症的作用、以及对心肌细胞和中性粒细胞功能的影响。有望把成纤维细胞MR确定为作用靶点，为干预房颤纤维化提供新的药物靶向证据和理论基础。

Atrial fibrillation (AF) result in atrial fibrosis, which also induced maintain mechanism of AF, these would form a vicious circle. However, there is no valid way to prevention and treatment. Studies from our group and others have demonstrated that mineralocorticoid receptor (MR) is a key player in atrial fibrosis through atrial fibroblast, but its roles in atrial fibrosis is not completely delineated. Therefore, we hypothesize that fibroblast MR controls atrial fibrosis through AngII/TGF-β signaling pathways and cell-cell interactions. We will use self-innovated cell-specific gene knockout or overexpression mouse, combination with atrium-specific fibrosis mouse model, to study how fibroblast MR affects the AngII/AT1R and TGF-β/SMAD pathways, inflammation, and further affect the function of cardiomyocytes and neutrophils via method of cellular and molecular biology as well as electrophysiology. The outcome of these studies may identify fibroblast MR as a therapeutic target, providing new strategies for intervention of atrial fibrosis in a cell type-specific manner.