Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair
Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair
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DOI：
10.1073/pnas.0610024104
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发表时间：
2007-01-30
影响因子：
11.1
通讯作者：
Dzau, Victor
中科院分区：
文献类型：
--
作者：
Mirotsou, Maria;Zhang, Zhongyan;Dzau, Victor
干细胞疗法已成为治疗多种疾病的一种有前景的工具。此前我们已经表明，Akt修饰的间充质干细胞通过旁分泌机制介导组织修复。通过一种全面的功能基因组策略，我们发现分泌型卷曲相关蛋白2（Sfrp2）是介导缺血性损伤后心肌存活和修复的关键干细胞旁分泌因子。已知Sfrp2可调节Wnt信号通路，并且我们证明，用分泌型卷曲相关蛋白处理的心肌细胞会增加细胞内β -连环蛋白，并上调抗凋亡基因的表达。这些发现揭示了Sfrp2在介导Akt -间充质干细胞对组织修复的旁分泌作用中所起的关键作用，并确定Wnt信号通路的调节可作为心脏病的一个治疗靶点。
Stem cell therapy has emerged as a promising tool for the treatment of a variety of diseases. Previously, we have shown that Akt-modified mesenchymal stem cells mediate tissue repair through paracrine mechanisms. Using a comprehensive functional genomic strategy, we show that secreted frizzled related protein 2 (Sfrp2) is the key stem cell paracrine factor that mediates myocardial survival and repair after ischemic injury. Sfrp2 is known to modulate Wnt signaling, and we demonstrate that cardiomyocytes treated with secreted frizzled related protein increase cellular beta-catenin and up-regulate expression of antiapoptotic genes. These findings reveal the key role played by Sfrp2 in mediating the paracrine effects of Akt-mesenchymal stem cells on tissue repair and identify modulation of Wnt signaling as a therapeutic target for heart disease.