| 김광일¹ ² ³, 조현주², 한주용¹ ² ⁴, 김태연² , 최동주¹ ² ³ ,김효수¹ ² ⁴,김철호¹ ² ³ ,오병희¹ ² ⁴, 박영배¹ ² ⁴ |
Objective: β-Catenin signaling plays a critical role in directing cell fate during embryogenesis, and uncontrollable activation of β-catenin leads to various human cancers, suggesting its importance in cell survival and proliferation. However, little is known regarding its role in endothelial cell (EC) and skeletal muscle proliferation, and progenitor cell mobilization.
Methods and Results: Adenovirus-mediated β-catenin gene transfer enhanced ECs proliferation, protected ECs from serum-deprivation-induced apoptosis, and increased the capillary forming capabilities, which was completely blocked by inhibition of its nuclear translocation with NCadDC cotransfection. In addition, the increased proliferation of ECs by β-catenin was associated with increased expression of cyclin E2, but not cyclin D1. In skeletal muscle cells, β-catenin overexpression increased proliferation with cyclin D1 expression, decreased apoptosis, and induced hypertrophy. Furthermore, β-catenin induced the expression of VEGF in skeletal muscle cells, resulting in EC proliferation. In a mouse hindlimb ischemia model, β-catenin gene transfer significantly increased recovery of blood perfusion, capillary density along with enhanced VEGF expression, and number of proliferating ECs and myocytes. Local delivery of β-catenin gene also promotes angiogenic progenitor cell mobilization from bone marrow and increases the number of satellite cells in muscle.
Conclusion: β-Catenin may be an important modulator of angiogenesis and myocyte regeneration in ischemic tissue not only by directly enhancing proliferation and survival of ECs and skeletal myocytes, but also by inducing VEGF expression and promoting angiogenic progenitor cell mobilization and muscle progenitor cell activation.
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