TGF-ß1-Containing exosomes from injured epithelial cells activate fibroblasts to initiate tissue regenerative responses and fibrosis

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Borges, FT (Author) Other; Melo, SA (Author) Other; Ozdemir, BC (Author) Other; Kato, N (Author) Other; Revuelta, I (Author) Other; Miller, CA (Author) Other; Gattone, VH (Author) Other; LeBleu, VS (Author) Other; Kalluri, R (Author) Other

Journal

Title: Journal of the American Society of Nephrology

Vol. 24

Pages: 385-392

ISSN: 1046-6673

Publisher: American Society of Nephrology

Indexing

Scopus - 269 Citations

Other information

Authenticus ID: P-00F-XPE

DOI: 10.1681/asn.2012101031

Abstract (EN): 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, a-smooth muscle actin expression, F-actin expression, and type I collagen production in fibroblasts. Fibroblast activation is dependent on exosomes delivering TGF-b1 mRNA among other yet to be identified moieties. This study suggests that TGF-b1 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.Copyright © 2013 by the American Society of Nephrology.

Language: English

Type (Professor's evaluation): Scientific