Hepatocyte-Derived Extracellular Vesicles Deliver miR-328-3p to Trigger PP2A-B56δ-Mediated p-NLRP3^S295-Dependent Metaflammation in Macrophages upon Microcystin-LR Exposure.

ABSTRACT: Microcystin-LR (MC-LR) exacerbates metabolic dysfunction-associated steatotic liver disease (MASLD) by inducing histopathological damage and lipid metabolism disorders. Inducible hepatocyte-derived extracellular vesicles (iHD-EVs) released after xenobiotic exposure activate the macrophage NOD-like receptor protein 3 (NLRP3) inflammasome. Suppression of NLRP3 phosphorylation at serine 295 (p-NLRP3^S295) is previously shown to alleviate MASLD progression. Here, it is demonstrated that microcystin-LR (MC-LR)-induced iHD-EVs reduced deliver of miR-328-3p to macrophages, thereby upregulating protein phosphatase 2A (PP2A)-B56δ. Consequent PP2A-B56δ activation disrupts inositol 1,4,5-triphosphate receptor and voltage-dependent anion channel 1 coupling, evokes mitochondria-associated end

SUBMITTER: Wu JS 

PROVIDER: S-EPMC12866802 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature