Effects of Exosomes Derived From Helicobacter pylori Outer Membrane Vesicle-Infected Hepatocytes on Hepatic Stellate Cell Activation and Liver Fibrosis Induction

Abstract

Liver fibrosis is a multifactorial disease with microbial and non-microbial causes. In recent years, <i>Helicobacter pylori</i> infection has been thought to play a critical role in some extra-gastrointestinal manifestations especially liver disorders. Outer membrane vesicles (OMVs) are one of the most important discussed <i>H. pylori</i> virulence factors. In the current study, four different clinical strains of <i>H. pylori</i> were collected and their OMVs were purified using ultra-centrifugation. To investigate their effects on liver cell exosomes, co-incubation with hepatocytes was applied. After a while, hepatocyte-derived exosomes were extracted and incubated with hepatic stellate cells (HSCs) to investigate the HSC activation and fibrosis marker induction. The expression of α-SMA, TIMP-1, β-catenin, vimentin, and e-cadherin messenger RNAs (mRNA) was assessed using real-time RT-PCR, and the protein expression of α-SMA, TIMP-1, β-catenin, vimentin, and e-cadherin was evaluated by Western blotting. Our results showed that infected hepatocyte-derived exosomes induced the expression of α-SMA, TIMP-1, β-catenin, and vimentin in HSCs and e-cadherin gene and protein expression was downregulated. In the current study, we found that <i>H. pylori</i>-derived OMVs may aid the exosome alternation and modified exosomes may have a possible role in HSC activation and liver fibrosis progression.