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Enhancement of LymphangiogenesisIn Vitrovia the Regulations of HIF-1αExpression and Nuclear Translocation by Deoxyshikonin

Authors :
Akiko Inujima
Keiichi Koizumi
Yoshiko Igarashi
Orawin Prangsaengtong
Jun Yeon Park
Naotoshi Shibahara
Source :
Evidence-Based Complementary and Alternative Medicine. 2013:1-11
Publication Year :
2013
Publisher :
Hindawi Limited, 2013.

Abstract

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-dependentin vitrocord 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-1αmRNA level, HIF-1αprotein level, and the accumulation of HIF-1αin the nucleus. Knockdown of the HIF-1αgene by transfection with siHIF-1αdecreased 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-1αknockdown cells. This indicated that deoxyshikonin induction of VEGF-C mRNA expression and cord formation in HMVEC-dLy on Matrigel occurred mainly via HIF-1αregulation. We also found that deoxyshikonin promoted wound healingin vitroby 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-1α. The findings suggest that deoxyshikonin may be a new drug candidate for wound healing and treatment of lymphatic diseases.

Details

ISSN :
17414288 and 1741427X
Volume :
2013
Database :
OpenAIRE
Journal :
Evidence-Based Complementary and Alternative Medicine
Accession number :
edsair.doi...........12c3edf6da61ee3cc13d20d57345f2f6
Full Text :
https://doi.org/10.1155/2013/148297