Endosomal signalling via exosome surface TGFβ-1

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Ganesh Vilas Shelke, Univ Gothenburg, University of Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Surg
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  • Yanan Yin, Shanghai Jiao Tong Univ, Shanghai Jiao Tong University, Sch Med, Dept Biochem & Mol Cell Biol, Univ Gothenburg, University of Gothenburg, Inst Med, Krefting Res Ctr, Sahlgrenska Acad
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  • Su Chul Jang, Univ Gothenburg, University of Gothenburg, Inst Med, Krefting Res Ctr, Sahlgrenska Acad
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  • Cecilia Lasser, Univ Gothenburg, University of Gothenburg, Inst Med, Krefting Res Ctr, Sahlgrenska Acad
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  • Stefan Wennmalm, Royal Inst Technol KTH, Royal Institute of Technology, Dept Appl Phys, SciLife Lab, Expt Biomol Phys Grp
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  • Hans Jurgen Hoffmann
  • Li Li, Shanghai Jiao Tong Univ, Shanghai Jiao Tong University, Shanghai Peoples Hosp 1, Dept Lab Med
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  • Yong Song Gho, POSTECH Pohang Univ Sci & Technol, Pohang University of Science & Technology (POSTECH), Dept Life Sci
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  • Jonas Andreas Nilsson, Univ Gothenburg, University of Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Surg
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  • Jan Lotvall, Univ Gothenburg, University of Gothenburg, Inst Med, Krefting Res Ctr, Sahlgrenska Acad

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
JournalJournal of Extracellular Vesicles
Volume8
Issue1
ISSN2001-3078
DOIs
Publication statusPublished - 2019

    Research areas

  • 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

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