Abstract
The blood and lymphatic vascular systems are the two major circulatory systems in the skin. The skin continuously receives nutrients and oxygen through the blood vessels, whereas excess water and wastes in the skin are taken up by lymphatic vessels, so that together they maintain skin homeostasis. Despite the indispensable roles of the lymphatic and blood vascular systems in the skin, very few detailed studies have been conducted on their histology and/or functions. First, we analyzed the alteration of the blood and lymphatic vasculature that causes intrinsic aging. Our previous report revealed that pericyte-covered blood vessels are significantly reduced in aged skin. On the other hand, here we showed that lymphatic tight junctions which connect lymphatic endothelial cells (LEC) are looser in aged skin. These data suggest an unstable structure of the circulatory system in aged skin. To investigate the molecular mechanism (s) of blood and lymphatic vascular changes that occur in the skin with age, we evaluated the function of Tie2 (endothelium-specific receptor tyrosine kinase 2) , which is known to be crucial for blood vascular maturation. We have previously demonstrated that Tie2 also promotes the stabilization of lymphatic vessels as well as blood vessels. Surprisingly, we found an age-dependent downregulation of Tie2 activation. This result indicates that the down-regulation of Tie2 activation that occurs with age disables the function of the vasculature as “a nutrient delivery and waste uptake system”. Finally, we found that Cinnamomum cassia Blume (Cinnamon) has a powerful potential to directly activate Tie2 in LEC. In addition, we isolated the Tie2 activating compound from Cinnamomum cassia Blume and determined the structure of the isolated compound as Syringaresinol. The activation of Tie2 induced by Cinnamomum cassia Blume promotes the stabilization of the lymphatic and blood vasculature, and could serve as a revolutionary new strategy to prevent skin aging because it directly counteracts alterations in those systems which disrupt the maintenance of skin homeostasis.
