Journal
JOURNAL OF EXTRACELLULAR VESICLES
Volume 8, Issue 1, Pages -Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/20013078.2019.1650458
Keywords
Mast cells; extracellular vesicles; exosomes; mesenchymal stem cells; tumour growth factor beta-1; cellular localization; endosomal signalling; proteoglycan
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Funding
- VBG group Herman Krefting Foundation for Allergy and Asthma Research
- Swedish Cancer Foundation [CAN2014/844]
- Swedish Research Council [2016-02854]
- Swedish Heart-Lung Foundation [2015-0588]
- European Academy of Allergy and Clinical Immunology
- Assar Gabrielssons Foundation [FB16-104]
- Stiftelserna Wilhelm and Martina Lundgrens [2017-1842]
- Sahlgrenska Academy
- Sahlgrenska University Hospital
- Swedish Research Council [2016-02854] Funding Source: Swedish Research Council
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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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