TGF-β1–Containing Exosomes from Injured Epithelial Cells Activate Fibroblasts to Initiate Tissue Regenerative Responses and Fibrosis
Top Cited Papers
- 1 March 2013
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of the American Society of Nephrology
- Vol. 24 (3), 385-392
- https://doi.org/10.1681/asn.2012101031
Abstract
Hypoxia is associated with tissue injury and fibrosis but its functional role in fibroblast activation and tissue repair/regeneration is unknown. Using kidney injury as a model system, we demonstrate that injured epithelial cells produce an increased number of exosomes with defined genetic information to activate fibroblasts. Exosomes released by injured epithelial cells promote proliferation, α-smooth muscle actin expression, F-actin expression, and type I collagen production in fibroblasts. Fibroblast activation is dependent on exosomes delivering TGF-β1 mRNA among other yet to be identified moieties. This study suggests that TGF-β1 mRNA transported by exosomes constitutes a rapid response to initiate tissue repair/regenerative responses and activation of fibroblasts when resident parenchyma is injured. The results also inform potential utility of exosome-targeted therapies to control tissue fibrosis.Keywords
This publication has 28 references indexed in Scilit:
- Impaired Wound Healing in Hypoxic Renal Tubular Cells: Roles of Hypoxia-Inducible Factor-1 and Glycogen Synthase Kinase 3β/β-Catenin SignalingThe Journal of pharmacology and experimental therapeutics, 2011
- LMP1 association with CD63 in endosomes and secretion via exosomes limits constitutive NF-κB activationThe EMBO Journal, 2011
- Role of Proximal Tubules in the Pathogenesis of Kidney DiseasePublished by S. Karger AG ,2011
- Tubular toxicity of proteinuriaNature Reviews Nephrology, 2010
- Sirt1 activation protects the mouse renal medulla from oxidative injuryJCI Insight, 2010
- Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transitionJCI Insight, 2007
- Systemic sclerosis: a prototypic multisystem fibrotic disorderJCI Insight, 2007
- Chronic kidney disease: A European perspectiveKidney International, 2005
- Myofibroblasts and mechano-regulation of connective tissue remodellingNature Reviews Molecular Cell Biology, 2002
- Molecules relevant for T cell‐target cell interaction are present in cytolytic granules of human T lymphocytesEuropean Journal of Immunology, 1989