分泌型卷曲相关蛋白2（Sfrp2）是介导心肌存活和修复的关键Akt-间充质干细胞释放的旁分泌因子。
Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair.
作者信息
Mirotsou Maria, Zhang Zhongyan, Deb Arjun, Zhang Lunan, Gnecchi Massimiliano, Noiseux Nicolas, Mu Hui, Pachori Alok, Dzau Victor
机构信息
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
出版信息
Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1643-8. doi: 10.1073/pnas.0610024104. Epub 2007 Jan 24.
Abstract
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.
摘要
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信号传导，并且我们证明用分泌型卷曲相关蛋白处理的心肌细胞可增加细胞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信号传导的调节作为心脏病的治疗靶点。
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本文引用的文献
1
Cardioprotective c-kit+ cells are from the bone marrow and regulate the myocardial balance of angiogenic cytokines.
J Clin Invest. 2006 Jul;116(7):1865-77. doi: 10.1172/JCI27019.
2
Myocardial-cell replacement: the science, the clinic and the future.
Nat Clin Pract Cardiovasc Med. 2004 Dec;1(2):90-5. doi: 10.1038/ncpcardio0051.
3
Overexpressed beta-catenin blocks nitric oxide-induced apoptosis in colonic cancer cells.
Cancer Res. 2005 Oct 1;65(19):8604-7. doi: 10.1158/0008-5472.CAN-05-1169.
4
Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells.
Nat Med. 2005 Apr;11(4):367-8. doi: 10.1038/nm0405-367.
5
Unchain my heart: the scientific foundations of cardiac repair.
J Clin Invest. 2005 Mar;115(3):572-83. doi: 10.1172/JCI24283.
6
The Wnt signaling pathway in development and disease.
Annu Rev Cell Dev Biol. 2004;20:781-810. doi: 10.1146/annurev.cellbio.20.010403.113126.
7
Statins inhibit reoxygenation-induced cardiomyocyte apoptosis: role for glycogen synthase kinase 3beta and transcription factor beta-catenin.
J Mol Cell Cardiol. 2004 Sep;37(3):681-90. doi: 10.1016/j.yjmcc.2004.05.025.
8
Bone-marrow-derived cells for enhancing collateral development: mechanisms, animal data, and initial clinical experiences.
Circ Res. 2004 Aug 20;95(4):354-63. doi: 10.1161/01.RES.0000137878.26174.66.
9
Molecular and cell-based therapies for protection, rescue, and repair of ischemic myocardium: reasons for cautious optimism.
Circulation. 2004 May 25;109(20):2386-93. doi: 10.1161/01.CIR.0000128597.37025.00.
10
Autocrine/paracrine secreted Frizzled-related protein 2 induces cellular resistance to apoptosis: a possible mechanism of mammary tumorigenesis.
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