Functional Effects of Extracellular Vesicles Altered by a Per- and Polyfluoroalkyl Substance Mixture: Liver Cell Proteomic Expression Alterations

ABSTRACT: Extracellular vesicles (EVs) have emerged as key molecules in cellular processes and diseases. The intersection of environmental exposures and EVs has recently gained attention, with EVs being highlighted as biomarkers of exposure, as well as mediators of environmental exposure-induced disease. The present study aims to evaluate whether EVs released from HepG2 liver cells can affect the biology of separate recipient HepG2 cells, measured through changes in global cellular protein expression. The hypothesis specifically evaluated in this study was that EVs released from PFAS-mixture treated liver cells are biologically active and will alter protein expression in separate liver cells related to chronic liver diseases and cancer. To evaluate this hypothesis, HepG2 cells representing “parent cells” were exposed to an equimolar PFAS mixture containing perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexanoic acid (PFHxA). EVs were isolated from parent cells and used to treat separate HepG2 liver cells, representing “target cells”, to evaluate changes in resulting proteomic expression profiles. Results from this demonstrated that EVs released from PFAS-treated HepG2 cells cause unique protein expression changes in separate HepG2 cells including numerous proteins associated with hepatic cancer, non-alcoholic fatty liver disease, and other hepatic diseases. These findings provide important context to previously observed changes in EV release and molecular content, highlighting the role EVs in a novel mechanism of PFAS-induced liver toxicity.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Angie Mordant  

LAB HEAD: Julia Rager

PROVIDER: PXD050095 | Pride | 2025-11-20

REPOSITORIES: Pride