Suppression Of Hepatic Stellate Cell Death By Toxic Advanced Glycation End-Products

Advanced glycation end-products (AGEs) are produced by the non-enzymatic reaction of sugars with proteins. It has been revealed that glyceraldehyde-derived toxic AGEs (TAGE) are elevated in the serum of non-alcoholic steatohepatitis (NASH) patients. NASH causes liver fibrosis and progresses to cirrhosis and hepatocellular carcinoma. However, the impact of TAGE in liver fibrosis caused by extracellular matrix accumulation remains poorly understood. In this study, we examined the effect of TAGE on the activation of hepatic stellate cells that are involved in liver fibrosis. LX-2 cells treated with transforming growth factor-beta 1 (TGF-beta 1) significantly reduced cell viability by apoptosis. However, the decrease in cell viability with TGF-beta 1 treatment was significantly suppressed by TAGE co-treatment. The levels of a-smooth muscle actin (alpha-SMA) and platelet-derived growth factor (PDGF)-R beta and its ligand PDGF-B were increased in LX-2 cells following TGF-beta 1 treatment, suggesting that these cells were activated; however, these increases were unaffected by TAGE co-treatment. Moreover, collagen I level was increased with TGF-beta 1 treatment, and this increase was further increased by TAGE co-treatment. These results suggested that the suppression of apoptosis in activated LX-2 cells by TGF-beta 1 and TAGE co-treatment is related to an increase in the production of the extracellular matrix such as collagen I. Therefore, it was suggested that TAGE might aggravate the liver fibrosis of chronic hepatitis, such as NASH.