Host: The Japanese Society of Toxicology
Name : The 51st Annual Meeting of the Japanese Society of Toxicology
Date : July 03, 2024 - July 05, 2024
Proteoglycans are composed of glycosaminoglycan(s) such as chondroitin/dermatan sulfate and heparan sulfate, a repeating structure of uronic acid and amino sugars, bound to a core protein. In vascular, proteoglycans are involved in the regulation of cell proliferation and the blood coagulation/fibrinolytic system. Vascular endothelial cells covering of the inner surface of blood vessels are locally exposed to a hypoxic environment when the vessel wall thickens in atherosclerosis. We have shown that the core protein expression of proteoglycans produced by vascular endothelial cells is altered under hypoxic conditions. The present study aimed to elucidate the effects of hypoxia on the gene expression of glycosaminoglycan synthase. Under hypoxic conditions, the expression of CHSY1, an elongating enzyme of chondroitin/dermatan sulfate, was decreased in sparse culture. Similarly, the expression of CHPF2, an elongating enzyme of chondroitin/dermatan sulfate chains, was downregulated regardless of cell density. On the other hand, the expression of EXT1, EXT2, and EXTL3, enzymes that elongate heparan sulfate, was suppressed in the dense culture at 8 h after hypoxia, while it turned to increase at 24 h. In the sparse culture, EXT1 expression increased at 8 h and decreased at 24 h after hypoxia, and EXT2 expression was continuously suppressed until 24 h after hypoxia. Future studies are needed to clarify the effects of these changes on protein expression and chain length of glycosaminoglycans.
