title: TGF-β1-containing exosomes from injured epithelial cells activate fibroblasts to initiate tissue regenerative responses and fibrosis.
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.
authors.affiliation: Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Fernanda T
authors.initials: FT
authors.lastname: Borges
authors.forename: Sonia A
authors.initials: SA
authors.lastname: Melo
authors.forename: Berna C
authors.initials: BC
authors.lastname: Özdemir
authors.forename: Noritoshi
authors.initials: N
authors.lastname: Kato
authors.forename: Ignacio
authors.initials: I
authors.lastname: Revuelta
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Miller
authors.forename: Vincent H
authors.initials: VH
authors.lastname: Gattone
authors.forename: Valerie S
authors.initials: VS
authors.lastname: LeBleu
authors.forename: Raghu
authors.initials: R
authors.lastname: Kalluri
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology; D055354:Exosomes / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D041681:NIH 3T3 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000235:genetics / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1