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Cell Biology and Toxicology

Cell Biology and Toxicology

IF: 5.3
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Human liver progenitor-like cells-derived extracellular vesicles promote liver regeneration during acute liver failure

Published:28 November 2024 DOI: 10.1007/s10565-024-09954-6 PMID: 39604571
Yi Chen,?Yuling Wu,?Hanyong Sun,?Hongdan Zhang,?Dan Tang,?Tianjie Yuan,?Caiyang Chen,?Weijian Huang,?Xu Zhou,?Hongping Wu,?Saihong Xu,?Wenming Liu,?Yingfu Jiao,?Liqun Yang,?Qigen Li,?Hexin Yan,?Weifeng Yu

Abstract

Hepatocyte-derived liver progenitor-like cells (HepLPCs) exhibit a remarkable capacity to support liver function by detoxifying ammonia, promoting native liver regeneration, and suppressing inflammation, which leads to improvements in the recovery and survival of animals with acute liver failure (ALF). However, the mechanism through which HepLPCs promote liver regeneration is unclear. Here, we isolated HepLPC-derived extracellular vesicles (HepLPC-EVs) from conditioned media and performed microRNA sequencing analysis. Our results showed HepLPC-EVs promoted liver regeneration in mice with carbon tetrachloride or acetaminophen induced ALF. Cell cycle progression and proliferation of primary human hepatocytes were promoted after coculture with HepLPC-EVs. Exosomal miRNA sequencing confirmed that HepLPC-EVs were enriched with miR-183-5p, which played an essential role in ameliorating ALF. Mechanistically, HepLPC-derived exosomal miR-183-5p negatively regulated the expression of the target gene FoxO1, activated the Akt/GSK3β/β-catenin signaling pathway, and thereby promoted liver regeneration and restoration of normal liver function. These results indicate that during ALF, HepLPC-Exos mediate liver regeneration mainly through a paracrine exosome-dependent mechanism and these effects accelerate liver regeneration and lead to the restoration of normal liver function.

Substances (6)

Materials
Procduct Name CAS Molecular Formula Supplier Price
A-83-01 909910-43-6 C25H19N5S 167 suppliers $10.00-$3420.00
A-83-01 909910-43-6 C25H19N5S 167 suppliers $10.00-$3420.00
A-83-01 909910-43-6 C25H19N5S 167 suppliers $10.00-$3420.00
A-83-01 909910-43-6 C25H19N5S 167 suppliers $10.00-$3420.00
3-(6-methylpyridin-2-yl)-N-phenyl-4-quinolin-4-ylpyrazole-1-carbothioamide 909910-43-6 C25H19N5S - Inquiry
3-(6-methylpyridin-2-yl)-N-phenyl-4-quinolin-4-ylpyrazole-1-carbothioamide 909910-43-6 C25H19N5S - Inquiry

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