心脏纤维化
纤维化
骨膜炎
Wnt信号通路
细胞外基质
压力过载
心功能曲线
心肌纤维化
医学
细胞生物学
内科学
心力衰竭
生物
基因剔除小鼠
化学
肌成纤维细胞
内分泌学
炎症
下调和上调
转基因小鼠
连环素
肌肉肥大
成纤维细胞
心室重构
连环蛋白
天狼星红
信号转导
心肌肥大
体外
生物化学
作者
Fu-Li Xiang,Ming Fang,Katherine E. Yutzey
标识
DOI:10.1038/s41467-017-00840-w
摘要
Cardiac fibrosis is characterized by excessive extracellular matrix deposition that contributes to compromised cardiac function and potentially heart failure. Cardiac pressure overload resulting from trans-aortic constriction in mice leads to cardiac fibrosis and increased Wnt/β-catenin signaling in cardiac fibroblasts. Here, we conditionally induce β-catenin loss of function in resident cardiac fibroblasts using Tcf21 MerCreMer or in activated cardiac fibroblasts using periostin (Postn) MerCreMer . We show that β-catenin loss of function in cardiac fibroblasts after trans-aortic constriction significantly preserves cardiac function, and reduces interstitial fibrosis but does not alter the numbers of activated or differentiated cardiac fibroblasts in vivo. However, β-catenin is specifically required in resident cardiac fibroblasts for fibrotic excessive extracellular matrix gene expression and binds Col3a1 and Postn gene sequences in cultured cardiac fibroblasts after induction of Wnt signaling. Moreover, cardiomyocyte hypertrophy is blunted with cardiac fibroblast-specific loss of β-catenin after trans-aortic constriction in vivo. Thus, Wnt/β-catenin signaling in resident cardiac fibroblasts is required for excessive extracellular matrix gene expression and collagen deposition after trans-aortic constriction.Understanding the mechanisms causing cardiac fibrosis is key to prevention and therapy development of many heart diseases. Here, the authors show that Wnt/β-catenin signaling in resident cardiac fibroblasts is required for deposition of fibrotic extracellular matrix and the regulation of cardiomyocyte hypertrophy in a mouse model of heart fibrosis.
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