Published online Nov 21, 2021. doi: 10.3748/wjg.v27.i43.7509
Peer-review started: April 21, 2021
First decision: July 14, 2021
Revised: July 21, 2021
Accepted: September 14, 2021
Article in press: September 14, 2021
Published online: November 21, 2021
Both acute liver injury (ALI) and chronic liver injury (CLI) do not always cause noticeable signs and symptoms. Serum small extracellular vesicles (sEVs) have attracted tremendous interest due to their essential roles in intercellular communication and their diagnostic and therapeutic potential. The cargoes carried by sEVs represent a snapshot of the parental cells and change depending on the physiological and pathological states.
Serum sEVs and their small RNA (sRNA) cargoes could be promising biomarkers for the diagnosis of liver injury.
The present study aimed to characterize the dynamic changes of serum sEVs and their sRNA components during liver injury and to explore the effect of liver injury-related serum sEVs on hepatic macrophages.
Male C57BL/6 mice were treated with CCL4 to establish a mouse liver injury model for simulating ALI, CLI and recovery. Serum sEVs were obtained and characterized by transmission electron microscopy and nanoparticle tracking analysis. Serum sEV sRNAs were profiled by sRNA sequencing. Differentially expressed microRNAs (miRNAs) were compared to mouse liver-enriched miRNAs and previously reported circulating miRNAs related to human liver diseases. The biological significance was evaluated by Ingenuity Pathway Analysis of the altered sEV miRNAs and conditioned cultures of ALI serum sEVs with primary hepatic macrophages.
Both ALI and CLI changed the concentration and morphology of serum sEVs. The proportion of serum sEV miRNAs increased upon liver injury, with the liver as the primary contributor. The altered serum sEV miRNAs based on mouse study were consistent with human liver disease-related circulating miRNAs. We established serum sEV miRNA signatures for ALI and CLI and a panel of miRNAs (miR-122-5p, miR-192-5p, and miR-22-3p) as a common marker for liver injury. ALI serum sEVs decreased both CD86 and CD206 expression in monocyte-derived macrophages but increased CD206 expression in resident macrophages in vitro.
Serum sEVs acquired different concentrations, sizes, morphologies and sRNA contents upon diverse liver injured pathological processes. ALI serum sEVs reprogrammed hepatic macrophage subgroups differently.
Serum sEVs have good diagnostic and therapeutic potential for liver injury.