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Wnt1 Inhibits Hydrogen Peroxide-Induced Apoptosis in Mouse Cardiac Stem Cells

2013; Public Library of Science; Volume: 8; Issue: 3 Linguagem: Inglês

10.1371/journal.pone.0058883

1932-6203

Jingjin Liu, Yongshun Wang, Wenjuan Du, Wenhua Liu, Fang Liu, Lulu Zhang, Maomao Zhang, Meng Hou, Kai Liu, Shuo Zhang, Bo Yu,

Cancer-related gene regulation

Background Because of their regenerative and paracrine abilities, cardiac stem cells (CSCs) are the most appropriate, optimal and promising candidates for the development of cardiac regenerative medicine strategies. However, native and exogenous CSCs in ischemic hearts are exposed to various pro-apoptotic or cytotoxic factors preventing their regenerative and paracrine abilities. Methods and Results We examined the effects of H2O2 on mouse CSCs (mCSCs), and observed that hydrogen peroxide (H2O2) treatment induces mCSCs apoptosis via the caspase 3 pathway, in a dose-dependent manner. We then examined the effects of Wnt1 over-expression on H2O2-induced apoptosis in mCSCs and observed that Wnt1 significantly decreased H2O2-induced apoptosis in mCSCs. On the other hand, inhibition of the canonical Wnt pathway by the secreted frizzled related protein 2 (SFRP2) or knockdown of β-catenin in mCSCs reduced cells resistance to H2O2-induced apoptosis, suggesting that Wnt1 predominantly prevents H2O2-induced apoptosis through the canonical Wnt pathway. Conclusions Our results provide the first evidences that Wnt1 plays an important role in CSCs’ defenses against H2O2-induced apoptosis through the canonical Wnt1/GSK3β/β-catenin signaling pathway.