Endoglin Trafficking/Exosomal Targeting in Liver Cells Depends on N-Glycosylation

Cells. 2019 Aug 28;8(9):997. doi: 10.3390/cells8090997.


Injury of the liver involves a wound healing partial reaction governed by hepatic stellate cells and portal fibroblasts. Individual members of the transforming growth factor-β (TGF-β) superfamily including TGF-β itself and bone morphogenetic proteins (BMP) exert diverse and partially opposing effects on pro-fibrogenic responses. Signaling by these ligands is mediated through binding to membrane integral receptors type I/type II. Binding and the outcome of signaling is critically modulated by Endoglin (Eng), a type III co-receptor. In order to learn more about trafficking of Eng in liver cells, we investigated the membranal subdomain localization of full-length (FL)-Eng. We could show that FL-Eng is enriched in Caveolin-1-containing sucrose gradient fractions. Since lipid rafts contribute to the pool of exosomes, we could consequently demonstrate for the first time that exosomes isolated from cultured primary hepatic stellate cells and its derivatives contain Eng. Moreover, via adenoviral overexpression, we demonstrate that all liver cells have the capacity to direct Eng to exosomes, irrespectively whether they express endogenous Eng or not. Finally, we demonstrate that block of N-glycosylation does not interfere with dimerization of the receptor, but abrogates the secretion of soluble Eng (sol-Eng) and prevents exosomal targeting of FL-Eng.

Keywords: BMP; Caveolin-1; TGF-β; endoglin; exosomes; fibrosis; hepatic stellate cells; hepatocytes; lipid raft; liver; portal myofibroblasts; shedding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / metabolism
  • Cell Line
  • Endoglin / physiology*
  • Exosomes / metabolism*
  • Hepatic Stellate Cells / cytology
  • Hepatic Stellate Cells / metabolism*
  • Hepatocytes / cytology
  • Hepatocytes / metabolism*
  • Humans
  • Liver / cytology
  • Liver / metabolism
  • Male
  • Mice
  • Protein Transport
  • Rats
  • Rats, Sprague-Dawley
  • Transforming Growth Factor beta / metabolism


  • Bone Morphogenetic Proteins
  • ENG protein, human
  • Endoglin
  • Eng protein, mouse
  • Eng protein, rat
  • Transforming Growth Factor beta