Beta-catenin overexpression augments angiogenesis and skeletal muscle regeneration through dual mechanism of vascular endothelial growth factor-mediated endothelial cell proliferation and progenitor cell mobilization.
OBJECTIVE
Beta-catenin plays a critical role in directing cell fate during embryogenesis, and uncontrollable activation leads to 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.


RESULTS
Beta-catenin enhanced ECs proliferation, protected ECs from apoptosis, and increased the capillary forming capabilities, which was completely blocked by inhibition of its nuclear translocation. In addition, the increased proliferation by beta-catenin was associated with increased expression of cyclin E2. In skeletal myocytes, beta-catenin overexpression increased proliferation with cyclin D1 expression, decreased apoptosis, and induced hypertrophy. Furthermore, beta-catenin induced the expression of vascular endothelial growth factor (VEGF) in skeletal myocytes, resulting in EC proliferation. In a mouse hindlimb ischemia model, beta-catenin significantly increased recovery of blood perfusion, capillary density along with enhanced VEGF expression, and the number of proliferating ECs and myocytes. Local delivery of beta-catenin also promoted angiogenic progenitor cell mobilization and increased the number of satellite cells.


CONCLUSIONS
Beta-catenin may be an important modulator of angiogenesis and myocyte regeneration 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.
Kim
Kwang-il
KI
Department of Internal Medicine, Seoul National University College of Medicine, Korea.
Cho
Hyun-Ju
HJ
Hahn
Joo-Yong
JY
Kim
Tae-Youn
TY
Park
Kyung-Woo
KW
Koo
Bon-Kwon
BK
Shin
Chan Soo
CS
Kim
Cheol-Ho
CH
Oh
Byung-Heeh
BH
Lee
Myoung-Mook
MM
Park
Young-Bae
YB
Kim
Hyo-Soo
HS
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D018014:Gene Transfer Techniques; D006614:Hindlimb; D006801:Humans; D006984:Hypertrophy; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000502:physiology; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D012038:Regeneration / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D014471:Umbilical Veins / Q000166:cytology; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
D051176:beta Catenin