title: Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair.
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.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Mirotsou
authors.forename: Zhongyan
authors.initials: Z
authors.lastname: Zhang
authors.forename: Arjun
authors.initials: A
authors.lastname: Deb
authors.forename: Lunan
authors.initials: L
authors.lastname: Zhang
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Gnecchi
authors.forename: Nicolas
authors.initials: N
authors.lastname: Noiseux
authors.forename: Hui
authors.initials: H
authors.lastname: Mu
authors.forename: Alok
authors.initials: A
authors.lastname: Pachori
authors.forename: Victor
authors.initials: V
authors.lastname: Dzau
mesh_terms: D000818:Animals; D002470:Cell Survival; D005260:Female; D020869:Gene Expression Profiling; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*; D015854:Up-Regulation; D051176:beta Catenin / Q000378:metabolism; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D008565:Membrane Proteins; D051057:Proto-Oncogene Proteins c-akt; D051176:beta Catenin; C491628:Sfrp2 protein, mouse; D000094742:Secreted Frizzled-Related Proteins; C503650:Sfrp2 protein, rat