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Title: Enhancement of lymphangiogenesis in vitro via the regulations of HIF-1 α expression and nuclear translocation by deoxyshikonin
Authors: Prangsaengtong O.
Park J.Y.
Inujima A.
Igarashi Y.
Shibahara N.
Koizumi K.
Keywords: deoxyshikonin
hypoxia inducible factor 1alpha
messenger RNA
shikonin derivative
unclassified drug
vasculotropin C
cell function
controlled study
drug mechanism
endothelium cell
gene expression regulation
gene silencing
gene translocation
genetic transfection
human cell
in vitro study
priority journal
protein expression
Issue Date: 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-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-1α mRNA level, HIF-1α protein level, and the accumulation of HIF-1α in the nucleus. Knockdown of the HIF-1α gene by transfection with siHIF-1α 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-1α knockdown cells. This indicated that deoxyshikonin induction of VEGF-C mRNA expression and cord formation in HMVEC-dLy on Matrigel occurred mainly via HIF-1α 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-1α. The findings suggest that deoxyshikonin may be a new drug candidate for wound healing and treatment of lymphatic diseases. © 2013 Orawin Prangsaengtong et al.
ISSN: 1741427X
Appears in Collections:Scopus 1983-2021

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