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Endosomal signalling via exosome surface TGF beta-1

Journal article
Authors Ganesh V Shelke
Yanan Yin
Su Chul Jang
Cecilia Lässer
S. Wennmalm
H. J. Hoffmann
L. Li
Y. S. Gho
Jonas A Nilsson
Jan Lötvall
Published in Journal of Extracellular Vesicles
Volume 8
Issue 1
Publication year 2019
Published at Institute of Clinical Sciences, Department of Surgery
Krefting Research Centre
Language en
Keywords Mast cells, extracellular vesicles, exosomes, mesenchymal stem cells, tumour growth factor beta-1, cellular localization, endosomal signalling, proteoglycan, mesenchymal stem-cells, heparan-sulfate proteoglycans, growth-factor-beta, tgf-beta, mediated transfer, cancer exosomes, internalization, fibroblast, phenotype, migration, Cell Biology
Subject categories Cell biology


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 beta-1 (TGF beta-1) on their surfaces. The latent form of TGF beta-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 TGF beta-1 is retained within the endosomal compartments at the time of signalling, which results in prolonged cellular signalling compared to free-TGF beta-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 TGF beta-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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