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Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
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Exosomes are stable, lipid bilayer-enclosed vesicles capable of crossing biological barriers. They can carry a wide range of molecules required for intercellular communication. Once exosomes are released from the cell where they originated, they enter a recipient cell through various pathways such as fusion, receptor-mediated endocytosis, macropinocytosis, and phagocytosis.
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Hormones—or any molecule that binds to a receptor, known as a ligand—that are lipid-insoluble (water-soluble) are not able to diffuse across the cell membrane. In order to be able to affect a cell without entering it, these hormones bind to receptors on the cell membrane. When a first messenger, a hormone, binds to a receptor, a signal cascade is set off, causing second messengers, proteins inside the cell, to become activated, resulting in downstream effects.
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Autocrine signaling is one of the many signaling mechanisms that function inside multicellular organisms to carry out intercellular communication. In this type of signaling mechanism, the same cell that secretes an extracellular signaling molecule also expresses the receptors to bind and respond to that signaling molecule.
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Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
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Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
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Endosomal signalling via exosome surface TGFβ-1.

Ganesh Vilas Shelke1,2, Yanan Yin1,3, Su Chul Jang1

  • 1Krefting Research Centre, Institute of Medicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Journal of Extracellular Vesicles
|October 10, 2019
PubMed
Summary

Mast cell exosomes carry latent transforming growth factor β-1 (TGFβ-1) on their surfaces. These exosomes are taken up by mesenchymal stem cells (MSCs), promoting MSC migration via sustained endosomal signaling.

Keywords:
Mast cellscellular localizationendosomal signallingexosomesextracellular vesiclesmesenchymal stem cellsproteoglycantumour growth factor beta-1

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Area of Science:

  • Cell Biology
  • Biochemistry
  • Immunology

Background:

  • Extracellular vesicles, including exosomes, mediate intercellular communication.
  • Transforming growth factor β-1 (TGFβ-1) plays critical roles in cell function and differentiation.
  • Mast cells and mesenchymal stem cells (MSCs) are involved in tissue repair and immune responses.

Purpose of the Study:

  • To investigate the role of mast cell-derived exosomes in delivering TGFβ-1 to recipient cells.
  • To determine the mechanism of TGFβ-1 association with exosomes and its fate in recipient cells.
  • To assess the functional impact of exosome-mediated TGFβ-1 delivery on MSCs.

Main Methods:

  • Isolation and characterization of exosomes from mast cells.
  • Analysis of TGFβ-1 association with exosomes using biochemical assays.
  • Tracking exosome uptake and intracellular localization in human MSCs via microscopy.
  • Assessment of MSC migration and SMAD pathway activation following exosome exposure.

Main Results:

  • Mast cell exosomes were found to carry both active and latent TGFβ-1 on their surface.
  • Latent TGFβ-1 was associated with exosomes via heparinase-II and pH-sensitive interactions.
  • Exosomes were rapidly internalized by MSCs, with TGFβ-1 retained within endosomal compartments.
  • Exosome-delivered TGFβ-1 induced prolonged signaling and promoted MSC migration through SMAD-dependent pathways.

Conclusions:

  • Mast cell-derived exosomes act as carriers for latent TGFβ-1, delivering it to recipient MSCs.
  • The endosomal retention of exosome-associated TGFβ-1 enhances and prolongs cellular signaling.
  • Exosomes facilitate intercellular communication by delivering bioactive surface ligands to intracellular compartments, influencing recipient cell behavior.