The anti-apoptotic effect of IGF-1 on tissue resident stem cells is mediated via PI3-kinase dependent secreted frizzled related protein 2 (Sfrp2) release.
Previous studies suggest that IGF-1 may be used as an adjuvant to stem cell transfer in order to improve cell engraftment in ischemic tissue. In the current study, we investigated the effect of IGF-1 on serum deprivation and hypoxia induced stem cell apoptosis and the possible mechanisms involved. Exposure of adipose tissue derived stem cells (ASCs) to serum deprivation and hypoxia resulted in significant apoptosis in ASC which is partially prevented by IGF-1. IGF-1's anti-apoptotic effect was abolished in ASCs transfected with Sfrp2 siRNA but not by the control siRNA. Using Western blot analysis, we demonstrated that serum deprivation and hypoxia reduced the expression of nuclear beta-catenin, which is reversed by IGF-1. IGF-1's effect on beta-catenin expression was abolished by the presence of PI3-kinase inhibitor LY294002 or in ASCs transfected with Sfrp2 siRNA. These results suggest that IGF-1, through the release of the Sfrp2, contributes to cell survival by stabilizing beta-catenin.
Gehmert
Sebastian
S
Department of Molecular Pathology, University of Texas M.D. Anderson Cancer Center, SCRB2, Box 951, 7435 Fannin Street, Houston, TX 77030, USA.
Sadat
Sanga
S
Song
Yao-Hua
YH
Yan
Yasheng
Y
Alt
Eckhard
E
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015687:Cell Hypoxia; D002470:Cell Survival; D002867:Chromones / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*; D000094742:Secreted Frizzled-Related Proteins
D002867:Chromones; D007334:Insulin-Like Growth Factor I; D008565:Membrane Proteins; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051176:beta Catenin; C491628:Sfrp2 protein, mouse; D000094742:Secreted Frizzled-Related Proteins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one