Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair.
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.
Mirotsou
Maria
M
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Zhang
Zhongyan
Z
Deb
Arjun
A
Zhang
Lunan
L
Gnecchi
Massimiliano
M
Noiseux
Nicolas
N
Mu
Hui
H
Pachori
Alok
A
Dzau
Victor
V
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
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