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 α
mRNA level, HIF-1 α
protein level, and the accumulation of HIF-1 α in the nucleus. Knockdown of the HIF-1 α gene by transfection with siHIF-1 α 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 α knockdown cells. This indicated that
deoxyshikonin induction of
VEGF-C mRNA expression and cord formation in HMVEC-dLy on
Matrigel occurred mainly via HIF-1 α 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 α . The findings suggest that
deoxyshikonin may be a new
drug candidate for wound healing and treatment of
lymphatic diseases.