Hepatic expression of galectin-3 and receptor for advanced glycation end products in patients with liver disease

Abstract

Background: Advanced glycation end products (AGEs) are a heterogeneous group of glycosylated proteins (of which carboxymethyl-lysine (CML) is the most common) which accumulate during ageing processes and play an important role in the pathogenesis of a variety of chronic diseases. Impaired hepatic function might result in elevated levels of AGEs, as the liver represents the major site of AGE metabolism. The actions of AGEs are mediated by various receptors, among which the AGE-receptor complex (including galectin-3 as an essential part) is thought to have a cytoprotective effect, and receptor for advanced glycation end product (RAGE) a cytotoxic effect. Aim: To assess the relationship between CML and expression of galectin-3 and RAGE in different histological structures in biopsy specimens from patients with varying degrees of liver impairment. Method: Immunohistochemical staining of 164 biopsies from patients with varying degrees of liver impairment was performed to determine the levels of CML, galectin-3 and RAGE in hepatocytes, Kupffer cells and bile ducts by a semiquantative score. Results: Independent of diagnosis, CML and RAGEs were detected in hepatocytes, whereas galectin-3 was present only in hepatocytes of cirrhotics. By contrast, CML and galectin-3 were highly expressed in Kupffer cells (well correlating levels, highest scores in cholestasis) whereas expression of RAGEs was not significant. All three assessed biochemical markers showed their highest levels of expression/detection in bile ducts. Conclusion: These findings indicate an increased susceptibility of hepatocytes to the detrimental effects of AGEs and underline the protective function of Kupffer cells. Furthermore, the biliary system seems to play an important role in the disposition of AGEs.

Impact of Androgen and Dietary Advanced Glycation End Products on Female Rat Liver

“…4) -possibly related to the increased glycotoxins deposition in intrahepatic biliary cells. Interestingly, this finding was also observed in previous studies indicating an important role of the biliary system in the disposition of AGE [21]. Furthermore, γGT levels were positively correlated with AGEs implying an aggravating impact of high AGE nutrition on this liver enzyme.…”

Multiple inflammatory-, tissue remodelling- and fibrosis genes are differentially transcribed in the livers ofAbcb4(−/ − ) mice harbouring chronic cholangitis

“…LGALS3 (Galectin3) is constitutively expressed in human intrahepatic bile ducts [30,31]. Expression of LGALS3 is induced in activated hepatic stellate cells where it acts together with LGALS1 to form an autocrine loop that induces proliferation of hepatic stellate cells [32].…”

Galectin-3 ablation protects mice from diet-induced NASH: A major scavenging role for galectin-3 in liver

“…However, endocytic uptake of AGEs by liver endothelial cells (LECs) was shown to be mediated by a receptor distinct from SR-A [16] and CD36 [18], but with closely similar ligand specificity. Receptor for AGEs (RAGE) is found predominantly in hepatocytes, whereas galectin-3 is highly expressed in Kupffer cells, and the levels of both receptors were reported to increase with the extent of liver damage [19]. RAGE blockade was shown to inhibit experimental hepatic fibrosis [20], whereas it was found to be up-regulated during HSC myofibroblast transdifferentiation [21].…”