Suppression of Hepatic Stellate Cell Death by Toxic Advanced Glycation End-Products
- 1 January 2021
- journal article
- research article
- Published by Pharmaceutical Society of Japan in Biological & Pharmaceutical Bulletin
- Vol. 44 (1), 112-117
- https://doi.org/10.1248/bpb.b20-00708
Abstract
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-β1 (TGF-β1) significantly reduced cell viability by apoptosis. However, the decrease in cell viability with TGF-β1 treatment was significantly suppressed by TAGE co-treatment. The levels of α-smooth muscle actin (α-SMA) and platelet-derived growth factor (PDGF)-Rβ and its ligand PDGF-B were increased in LX-2 cells following TGF-β1 treatment, suggesting that these cells were activated; however, these increases were unaffected by TAGE co-treatment. Moreover, collagen I level was increased with TGF-β1 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-β1 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.Keywords
This publication has 29 references indexed in Scilit:
- Role of advanced glycation end products (AGEs) and oxidative stress in vascular complications in diabetesBiochimica et Biophysica Acta (BBA) - General Subjects, 2012
- Atorvastatin decreases serum levels of advanced glycation endproducts (AGEs) in nonalcoholic steatohepatitis (NASH) patients with dyslipidemia: clinical usefulness of AGEs as a biomarker for the attenuation of NASHThe Esophagus, 2010
- The formation of intracellular glyceraldehyde-derived advanced glycation end-products and cytotoxicityThe Esophagus, 2010
- Elevated levels of serum advanced glycation end products in patients with non‐alcoholic steatohepatitisJournal of Gastroenterology and Hepatology, 2007
- Non-Smad TGF-β signalsJournal of Cell Science, 2005
- TAGE (toxic AGEs) hypothesis in various chronic diseasesMedical Hypotheses, 2004
- Reduced cell replication and induction of apoptosis by advanced glycation end products in rat Schwann cellsBiochemical and Biophysical Research Communications, 2004
- Long term prognosis of fatty liver: risk of chronic liver disease and deathGut, 2004
- Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndromeHepatology, 2003
- NASH and insulin resistance: Insulin hypersecretion and specific association with the insulin resistance syndromeHepatology, 2002