Extracellular Vesicles From Hepatocytes Are Therapeutic for Toxin-Mediated Fibrosis and Gene Expression in the Liver
| Autor: | David R. Brigstock, Ruju Chen, Xinlei Li, Sherri Kemper |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
extracellular matrix Extracellular matrix Cell and Developmental Biology 03 medical and health sciences 0302 clinical medicine Fibrosis Gene expression hepatocyte medicine exosome hepatic fibrosis lcsh:QH301-705.5 Original Research hepatic stellate cell Chemistry Cell Biology medicine.disease Cell biology CTGF 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) inflammation 030220 oncology & carcinogenesis Hepatocyte Hepatic stellate cell cell cycle extracellular vesicle Signal transduction Hepatic fibrosis Developmental Biology |
| Zdroj: | Frontiers in Cell and Developmental Biology Frontiers in Cell and Developmental Biology, Vol 7 (2020) |
| ISSN: | 2296-634X |
| 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) |
| Databáze: | OpenAIRE |
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