Extracellular Vesicles From Hepatocytes Are Therapeutic for Toxin-Mediated Fibrosis and Gene Expression in the Liver

Autor: Xinlei Li, Ruju Chen, Sherri Kemper, David R. Brigstock
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Frontiers in Cell and Developmental Biology, Vol 7 (2020)
Druh dokumentu: article
ISSN: 2296-634X
DOI: 10.3389/fcell.2019.00368
Popis: Extracellular vesicles (EVs) are nano-sized membrane-limited organelles that are liberated from their producer cells, traverse the intercellular space, and may interact with other cells resulting in the uptake of the EV molecular payload by the recipient cells which may become functionally reprogramed as a result. Previous in vitro studies showed that EVs purified from normal mouse AML12 hepatocytes (“EVNorm”) attenuate the pro-fibrogenic activities of activated hepatic stellate cells (HSCs), a principal fibrosis-producing cell type in the liver. In a 10-day CCl4 injury model, liver fibrogenesis, expression of hepatic cellular communication network factor 2 [CCN2, also known as connective tissue growth factor (CTGF)] or alpha smooth muscle actin (αSMA) was dose-dependently blocked during concurrent administration of EVNorm. Hepatic inflammation and expression of inflammatory cytokines were also reduced by EVNorm. In a 5-week CCl4 fibrosis model in mice, interstitial collagen deposition and mRNA and/or protein for collagen 1a1, αSMA or CCN2 were suppressed following administration of EVNorm over the last 2 weeks. RNA sequencing (RNA-seq) revealed that EVNorm therapy of mice receiving CCl4 for 5 weeks resulted in significant differences [false discovery rate (FDR)
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