Endosomal signalling via exosome surface TGFβ-1

Extracellular vesicles such as exosomes convey biological messages between cells, either by surface-to-surface interaction or by shuttling of bioactive molecules to a recipient cell’s cytoplasm. Here we show that exosomes released by mast cells harbour both active and latent transforming growth fact...

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Main Authors: Ganesh Vilas Shelke, Yanan Yin, Su Chul Jang, Cecilia Lässer, Stefan Wennmalm, Hans Jürgen Hoffmann, Li Li, Yong Song Gho, Jonas Andreas Nilsson, Jan Lötvall
Format: Article
Language:English
Published: Wiley 2019-12-01
Series:Journal of Extracellular Vesicles
Subjects:
Online Access:http://dx.doi.org/10.1080/20013078.2019.1650458
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author Ganesh Vilas Shelke
Yanan Yin
Su Chul Jang
Cecilia Lässer
Stefan Wennmalm
Hans Jürgen Hoffmann
Li Li
Yong Song Gho
Jonas Andreas Nilsson
Jan Lötvall
author_facet Ganesh Vilas Shelke
Yanan Yin
Su Chul Jang
Cecilia Lässer
Stefan Wennmalm
Hans Jürgen Hoffmann
Li Li
Yong Song Gho
Jonas Andreas Nilsson
Jan Lötvall
author_sort Ganesh Vilas Shelke
collection DOAJ
description Extracellular vesicles such as exosomes convey biological messages between cells, either by surface-to-surface interaction or by shuttling of bioactive molecules to a recipient cell’s cytoplasm. Here we show that exosomes released by mast cells harbour both active and latent transforming growth factor β-1 (TGFβ-1) on their surfaces. The latent form of TGFβ-1 is associated with the exosomes via heparinase-II and pH-sensitive elements. These vesicles traffic to the endocytic compartment of recipient human mesenchymal stem cells (MSCs) within 60 min of exposure. Further, the exosomes-associated TGFβ-1 is retained within the endosomal compartments at the time of signalling, which results in prolonged cellular signalling compared to free-TGFβ-1. These exosomes induce a migratory phenotype in primary MSCs involving SMAD-dependent pathways. Our results show that mast cell-derived exosomes are decorated with latent TGFβ-1 and are retained in recipient MSC endosomes, influencing recipient cell migratory phenotype. We conclude that exosomes can convey signalling within endosomes by delivering bioactive surface ligands to this intracellular compartment.
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spelling doaj.art-8a704db634814d7081d5caef3ccdb45a2022-12-21T18:41:58ZengWileyJournal of Extracellular Vesicles2001-30782019-12-018110.1080/20013078.2019.16504581650458Endosomal signalling via exosome surface TGFβ-1Ganesh Vilas Shelke0Yanan Yin1Su Chul Jang2Cecilia Lässer3Stefan Wennmalm4Hans Jürgen Hoffmann5Li Li6Yong Song Gho7Jonas Andreas Nilsson8Jan Lötvall9University of GothenburgUniversity of GothenburgUniversity of GothenburgUniversity of GothenburgExperimental Biomolecular Physics Group, SciLife LaboratoryAarhus UniversityShanghai First People’s Hospital, Shanghai JiaoTong UniversityPohang University of Science and TechnologyInstitute of Clinical Sciences, the Sahlgrenska Academy, University of GothenburgUniversity of GothenburgExtracellular vesicles such as exosomes convey biological messages between cells, either by surface-to-surface interaction or by shuttling of bioactive molecules to a recipient cell’s cytoplasm. Here we show that exosomes released by mast cells harbour both active and latent transforming growth factor β-1 (TGFβ-1) on their surfaces. The latent form of TGFβ-1 is associated with the exosomes via heparinase-II and pH-sensitive elements. These vesicles traffic to the endocytic compartment of recipient human mesenchymal stem cells (MSCs) within 60 min of exposure. Further, the exosomes-associated TGFβ-1 is retained within the endosomal compartments at the time of signalling, which results in prolonged cellular signalling compared to free-TGFβ-1. These exosomes induce a migratory phenotype in primary MSCs involving SMAD-dependent pathways. Our results show that mast cell-derived exosomes are decorated with latent TGFβ-1 and are retained in recipient MSC endosomes, influencing recipient cell migratory phenotype. We conclude that exosomes can convey signalling within endosomes by delivering bioactive surface ligands to this intracellular compartment.http://dx.doi.org/10.1080/20013078.2019.1650458mast cellsextracellular vesiclesexosomesmesenchymal stem cellstumour growth factor beta-1cellular localizationendosomal signallingproteoglycan
spellingShingle Ganesh Vilas Shelke
Yanan Yin
Su Chul Jang
Cecilia Lässer
Stefan Wennmalm
Hans Jürgen Hoffmann
Li Li
Yong Song Gho
Jonas Andreas Nilsson
Jan Lötvall
Endosomal signalling via exosome surface TGFβ-1
Journal of Extracellular Vesicles
mast cells
extracellular vesicles
exosomes
mesenchymal stem cells
tumour growth factor beta-1
cellular localization
endosomal signalling
proteoglycan
title Endosomal signalling via exosome surface TGFβ-1
title_full Endosomal signalling via exosome surface TGFβ-1
title_fullStr Endosomal signalling via exosome surface TGFβ-1
title_full_unstemmed Endosomal signalling via exosome surface TGFβ-1
title_short Endosomal signalling via exosome surface TGFβ-1
title_sort endosomal signalling via exosome surface tgfβ 1
topic mast cells
extracellular vesicles
exosomes
mesenchymal stem cells
tumour growth factor beta-1
cellular localization
endosomal signalling
proteoglycan
url http://dx.doi.org/10.1080/20013078.2019.1650458
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