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, Helicobacter pylori 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 H. pylori virulence factors. In the current study, four different clinical strains of H. pylori 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 H. pylori-derived OMVs may aid the exosome alternation and modified exosomes may have a possible role in HSC activation and liver fibrosis progression.

Extracellular vesicles from Lactobacillus druckerii inhibit hypertrophic scar fibrosis

“…We found that LDEVs can reduce Collagen I/III and α-SMA expression in HFBs, promote wound healing and inhibit scar formation. The researchers found that outer membrane vesicles (OMVs) derived from Helicobacter pylori -derived have a probable role in liver fibrosis progression [ 35 ]. Akkermansia muciniphila -secreted EVs can inhibit the expression of liver fibrosis markers [ 36 ].…”

Exosomes in liver fibrosis: The role of modulating hepatic stellate cells and immune cells, and prospects for clinical applications

“…Zahmatkesh et al. demonstrated that Exosomes derived from hepatocytes infected with helicobacter pylori outer membrane vesicle can lead to overexpression of HSC activation markers and fibrosis markers, suggesting a possible role in HSC activation and LF progression ( 42 ). Dai et al.…”

“…During hepatitis B virus (HBV) infection, exosomes derived from HBV-infected hepatocytes promote HSC activation and LF in mice. Among them, the exosomal miR-222 could enhance HSC activation by inhibiting transferrin receptor (TFRC)-induced HSC iron death (39). Exosomes from hepatitis C virus (HCV)infected hepatocytes can also induce HSC activation.…”

Differential Expression of α-Enolase in Clinical Gastric Tissues and Cultured Normal/Cancer Cells in Response to Helicobacter pylori Infection and cagA Transfection

“…Currently, it is known that H. pylori infection is closely related to a variety of gastrointestinal/extragastrointestinal diseases, including chronic superficial gastritis (CSG), chronic atrophic gastritis (CAG), intestinal metaplasia (IM), dysplasia, gastric cancer, liver cirrhosis, etc. [ 3 , 4 , 5 ]. However, host–microbe interactions behind these diseases (especially stomach cancer) remain poorly understood [ 3 , 4 , 5 ].…”

“…[ 3 , 4 , 5 ]. However, host–microbe interactions behind these diseases (especially stomach cancer) remain poorly understood [ 3 , 4 , 5 ]. This issue has been hindering the development of preventive and therapeutic strategies for these diseases.…”