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- Title
Annexin A1-containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair.
- Authors
Leoni, Giovanna; Neumann, Philipp-Alexander; Kamaly, Nazila; Quiros, Miguel; Hikaru Nishio; Jones, Hefin R.; Sumagin, Ronen; Hilgarth, Roland S.; Alam, Ashfaqul; Fredman, Gabrielle; Argyris, Ioannis; Rijcken, Emile; Kusters, Dennis; Reutelingsperger, Chris; Perretti, Mauro; Parkos, Charles A.; Farokhzad, Omid C.; Neish, Andrew S.; Nusrat, Asma
- Abstract
Epithelial restitution is an essential process that is required to repair barrier function at mucosal surfaces following injury. Prolonged breaches in epithelial barrierfunction result in inflammation and further damage; therefore, a better understanding of the epithelial restitution process has potential for improvingthe development of therapeutics. In this work, we demonstrate that endogenous annexin A1 (ANXA1) is released as a component of extracellular vesicles (EVs) derived from intestinal epithelial cells, and these ANXA1-containing EVs activate wound repair circuits. Compared with healthy controls, patients with active inflammatory bowel disease had elevated levels of secreted ANXA1-containing EVs in sera, indicating that ANXA1-containing EVs are systemically distributed in response to the inflammatory process and could potentially serve as a biomarker of intestinal mucosal inflammation. Local intestinal delivery of an exogenous ANXA1 mimetic peptide (Ac2-26) encapsulated within targeted polymeric nanoparticles (Ac2-26 Col IV NPs) accelerated healing of murine colonic wounds after biopsy-induced injury. Moreover, one-time systemic administration of Ac2-26 Col IV NPs accelerated recovery following experimentally induced colitis. Together, our results suggest that local delivery of proresolving peptides encapsulated within nanoparticles may represent a potential therapeutic strategy for clinical situations characterized by chronic mucosal injury, such as is seen in patients with IBD.
- Subjects
ANNEXINS; CALCIUM-binding proteins; INFLAMMATORY mediators; VESICLES (Cytology); ORGANELLES
- Publication
Journal of Clinical Investigation, 2015, Vol 125, Issue 3, p1215
- ISSN
0021-9738
- Publication type
Article
- DOI
10.1172/JCI76693