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Endosomal signalling via exosome surface TGF beta-1
Univ Gothenburg, Sahlgrenska Acad, Krefting Res Ctr, Inst Med, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Surg, Gothenburg, Sweden..
Univ Gothenburg, Sahlgrenska Acad, Krefting Res Ctr, Inst Med, Gothenburg, Sweden.;Shanghai Jiao Tong Univ, Sch Med, Dept Biochem & Mol Cell Biol, Shanghai, Peoples R China..
Univ Gothenburg, Sahlgrenska Acad, Krefting Res Ctr, Inst Med, Gothenburg, Sweden..ORCID iD: 0000-0003-3326-1007
Univ Gothenburg, Sahlgrenska Acad, Krefting Res Ctr, Inst Med, Gothenburg, Sweden..
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2019 (English)In: Journal of Extracellular Vesicles, ISSN 2001-3078, E-ISSN 2001-3078, Vol. 8, no 1, article id 1650458Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD , 2019. Vol. 8, no 1, article id 1650458
Keywords [en]
Mast cells, extracellular vesicles, exosomes, mesenchymal stem cells, tumour growth factor beta-1, cellular localization, endosomal signalling, proteoglycan
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:kth:diva-261929DOI: 10.1080/20013078.2019.1650458ISI: 000487027300001Scopus ID: 2-s2.0-85073213882OAI: oai:DiVA.org:kth-261929DiVA, id: diva2:1361311
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20191015

Available from: 2019-10-15 Created: 2019-10-15 Last updated: 2020-03-09Bibliographically approved

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Wennmalm, Stefan

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