Secreted frizzled related protein 2 protects cells from apoptosis by blocking the effect of canonical Wnt3a.
作者： Zhongyan Zhang , Arjun Deb , Zhiping Zhang , Alok Pachori , Wei He
DOI: 10.1016/J.YJMCC.2008.11.016
关键词:
摘要: We have demonstrated that mesenchymal stem cells overexpressing the survival gene Akt can confer paracrine protection to ischemic myocytes both in vivo and vitro through release of secreted frizzled related protein 2 (Sfrp2). However, mechanisms mediating these effects Sfrp2 not been fully elucidated. In this study, we studied rat cardiomyoblasts subjected hypoxia reoxygenation (HR) injury test hypothesis exerts anti-apoptotic effect by antagonizing pro-apoptotic properties specific Wnt ligands. examined Wnt3a on HR-induced apoptosis. significantly increased cellular caspase activities TUNEL staining response HR. attenuated Wnt3a-induced a concentration dependent fashion. Using solid phase binding assay, our data demonstrates physically binds Wnt3a. addition, observed dramatically inhibits beta-catenin/TCF transcriptional induced Impressively, Dickkopf-1, coreceptor LRP, inhibited Wnt3a-activated activities. Similarly, siRNA against beta-catenin markedly Consistent with this, fewer positive were transfected than control cells. Together, provide strong evidence support notion is canonical action whose activity prevented through, at least part, direct molecules. These results explain protective highlight its therapeutic potential for heart.
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