Transcriptome of extracellular vesicles released by hepatocytes

PLoS One. 2013 Jul 11;8(7):e68693. doi: 10.1371/journal.pone.0068693. Print 2013.

Abstract

The discovery that the cells communicate through emission of vesicles has opened new opportunities for better understanding of physiological and pathological mechanisms. This discovery also provides a novel source for non-invasive disease biomarker research. Our group has previously reported that hepatocytes release extracellular vesicles with protein content reflecting the cell-type of origin. Here, we show that the extracellular vesicles released by hepatocytes also carry RNA. We report the messenger RNA composition of extracellular vesicles released in two non-tumoral hepatic models: primary culture of rat hepatocytes and a progenitor cell line obtained from a mouse foetal liver. We describe different subpopulations of extracellular vesicles with different densities and protein and RNA content. We also show that the RNA cargo of extracellular vesicles released by primary hepatocytes can be transferred to rat liver stellate-like cells and promote their activation. Finally, we provide in vitro and in vivo evidence that liver-damaging drugs galactosamine, acetaminophen, and diclofenac modify the RNA content of these vesicles. To summarize, we show that the extracellular vesicles secreted by hepatocytes contain various RNAs. These vesicles, likely to be involved in the activation of stellate cells, might become a new source for non-invasive identification of the liver toxicity markers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Extracellular Matrix / genetics*
  • Hepatic Stellate Cells / cytology
  • Hepatic Stellate Cells / physiology
  • Hepatocytes / physiology*
  • Liver / cytology
  • Liver / physiology
  • Male
  • Mice
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cells / physiology
  • Transcriptome
  • Transport Vesicles / genetics*

Substances

  • RNA, Messenger

Grant support

This work was supported by grants from the Fondo de Investigaciones Sanitarias (Institute of Health Carlos III PS09/00526 and to JMF); Program “Ramon y Cajal” of Spanish Ministry (to JMF); Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd) is funded by the Institute of Health Carlos III. Research infrastructure was supported by the Department of Industry, Tourism and Trade of the Government of the Autonomous Community of the Basque Country (Etortek Research Programs 2010/2013) and the Innovation Technology Department of the Bizkaia County. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.