Changes in serum hyaluronic acid levels and expression of CD44 and CD44 mRNA in hepatic sinusoidal endothelial cells after major hepatectomy in cirrhotic rats.

Abstract

Serum hyaluronic acid (HA) is widely distributed in connective tissues, and the majority of circulating HA is degraded by hepatic sinusoidal endothelial cells (SECs) via a receptor recycling pathway. Our previous clinical study revealed that monitoring serum HA levels after hepatectomy is useful in predicting the development of liver failure. In the present study, to determine the mechanism of the high HA levels after hepatectomy, especially in patients with liver cirrhosis, expression of the major HA receptor, CD44, and its mRNA was investigated in SECs isolated from rats with thioacetamide-induced liver cirrhosis subjected to 70% hepatectomy (group I) and from rats with a normal liver that were subjected to 70% hepatectomy (group II). The 48-hour postoperative survival rate in group I (13.3%) was significantly lower than in group II (100%). In group II, the expression of CD44 mRNA had increased significantly at 6 hours after hepatectomy, and this was followed by progressive increases in expression of CD44, indicating activation of SEC function. The increased serum HA levels after hepatectomy in group II became normal as CD44 expression increased. By contrast, the expression of CD44 and CD44 mRNA in group I was markedly attenuated after hepatectomy. The very low CD44 expression was followed by a significant and sustained increase in serum HA levels, indicating functional failure of the SECs. These results suggest that the significantly impaired functional reserve of SECs in liver cirrhosis is associated with increased mortality after 70% hepatectomy.