Endosomal signalling via exosome surface TGFβ-1

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

Research output: Contribution to journalArticlepeer-review

80 Citations (Scopus)


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.

Original languageEnglish
Article number1650458
Pages (from-to)1650458
JournalJournal of Extracellular Vesicles
Issue number1
Publication statusPublished - 1 Dec 2019
Externally publishedYes


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