Enhancement of Lymphangiogenesis In Vitro via the Regulations of HIF-1α Expression and Nuclear Translocation by Deoxyshikonin

被引:15
作者
Prangsaengtong, Orawin [1 ,2 ]
Park, Jun Yeon [1 ]
Inujima, Akiko [1 ]
Igarashi, Yoshiko [1 ]
Shibahara, Naotoshi [1 ]
Koizumi, Keiichi [1 ]
机构
[1] Toyama Univ, Inst Nat Med, Dept Kampo Diagnost, Toyama 9300194, Japan
[2] Srinakharinwirot Univ, Fac Pharm, Dept Biopharm, Nakhonnayok 26120, Thailand
关键词
ENDOTHELIAL GROWTH-FACTOR; FACTOR-C; LITHOSPERMUM-ERYTHRORHIZON; ANGIOGENESIS; SHIKONIN; HYPOXIA; ACETYLSHIKONIN; PROLIFERATION; MIGRATION; SURVIVAL;
D O I
10.1155/2013/148297
中图分类号
R [医药、卫生];
学科分类号
10 ;
摘要
The objectives of this study were to determine the effects of deoxyshikonin on lymphangiogenesis. Deoxyshikonin enhanced the ability of human dermal lymphatic microvascular endothelial cells (HMVEC-dLy) to undergo time-dependent in vitro cord formation. Interestingly, an opposite result was observed in cells treated with shikonin. The increased cord formation ability following deoxyshikonin treatment correlated with increased VEGF-C mRNA expression to higher levels than seen for VEGF-A and VEGF-D mRNA expression. We also found that deoxyshikonin regulated cord formation of HMVEC-dLy by increasing the HIF-1 alpha mRNA level, HIF-1 alpha protein level, and the accumulation of HIF-1 alpha in the nucleus. Knockdown of the HIF-1 alpha gene by transfection with siHIF-1 alpha decreased VEGF-C mRNA expression and cord formation ability in HMVEC-dLy. Deoxyshikonin treatment could not recover VEGF-C mRNA expression and cord formation ability in HIF-1 alpha knockdown cells. This indicated that deoxyshikonin induction of VEGF-C mRNA expression and cord formation in HMVEC-dLy on Matrigel occurred mainly via H IF1 alpha regulation. We also found that deoxyshikonin promoted wound healing in vitro by the induction of HMVEC-dLy migration into the wound gap. This study describes a new effect of deoxyshikonin, namely, the promotion of cord formation by human endothelial cells via the regulation of HIF-1 alpha The findings suggest that deoxyshikonin may be a new drug candidate for wound healing and treatment of lymphatic diseases.
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页数:11
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