探討幽門螺旋桿菌感染胃上皮細胞時半乳糖凝集素-3與-8在細胞自嗜所扮演的角色

Abstract

Galectins, beta-galactoside-binding lectins, are known to exert various functions, including cell activation, growth, and apoptosis. In recent years, galectins were shown to regulate cellular autophagy response after sensing bacteria-induced vacuole lysis. Helicobacter (H.) pylori is a bacterium majorly found in the stomach and capable of activating autophagy in infected cells. In this thesis, we investigated the role of galectin-3 and -8 in gastric epithelial cells upon exposure to H. pylori. We found that H. pylori coculture increases intracellular aggregation of galectin-3 and -8 in human-derived AGS gastric epithelial cells. Notably, both galectin aggregates colocalize with lysosomes, and their aggregation is markedly reduced following the attenuation of host O-glycan processing. This indicates that H. pylori infection induces lysosomal damage, which in turn results in the accumulation of cytosolic galectin-3 and -8 around damaged lysosomes through the recognition of exposed vacuolar host O-glycans. H. pylori-induced galectin-8 aggregates may enhance autophagy activity in infected cells. While H. pylori-elicited galectin-3 aggregates may also execute a function on potentiating autophagy response, this functional effect is apparent only when cells are devoid of galectin-8 expression. We also found autophagy plays a part in facilitating H. pylori-mediated galectin-8 aggregation. Additionally, vacuolating cytotoxin A (VacA), a pore-forming H. pylori cytotoxin, contributes to the increased galectin-8 aggregation and elevated autophagy response in infected cells. Collectively, our results suggest that both galectin-3 and -8 promote host autophagy response following recognizing lysosomal injury induced by H. pylori, and that VacA may be a critical factor to destabilize lysosomal membrane during infection.