Annexin A1–containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair
Giovanna Leoni, … , Andrew S. Neish, Asma Nusrat
Giovanna Leoni, … , Andrew S. Neish, Asma Nusrat
Published February 9, 2015
Citation Information: J Clin Invest. 2015;125(3):1215-1227. https://doi.org/10.1172/JCI76693.
View: Text | PDF
Research Article Gastroenterology Article has an altmetric score of 5

Annexin A1–containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair

Abstract

Epithelial restitution is an essential process that is required to repair barrier function at mucosal surfaces following injury. Prolonged breaches in epithelial barrier function result in inflammation and further damage; therefore, a better understanding of the epithelial restitution process has potential for improving the 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.

Authors

Giovanna Leoni, Philipp-Alexander Neumann, Nazila Kamaly, Miguel Quiros, Hikaru Nishio, Hefin R. Jones, Ronen Sumagin, Roland S. Hilgarth, Ashfaqul Alam, Gabrielle Fredman, Ioannis Argyris, Emile Rijcken, Dennis Kusters, Chris Reutelingsperger, Mauro Perretti, Charles A. Parkos, Omid C. Farokhzad, Andrew S. Neish, Asma Nusrat

×

Figure 4

Serum-derived exosomes from healthy controls and patients with IBD.

Options: View larger image (or click on image) Download as PowerPoint
Serum-derived exosomes from healthy controls and patients with IBD. (A a...
(A and B) Immunoblots of ANXA1, CD9, and ANXA5 in isolated exosomes from sera of human (A) healthy controls and (B) patients with IBD. Exosomes were precipitated from human pooled sera using SBI’s Serum ExoQuick precipitation reagent (data are representative of n = 3 experiments). (C) Representative side scatter versus bright-field area (SSC/Ch12) and Ch04 fluorescence plots for EV isolates acquired with 1-μm and 500-nm reference beads (100-nm and 50-nm beads were acquired separately and overlaid) of EVs isolated from human sera by ultracentrifugation (n = 3). (D) Representative bright-field (Ch01), Ch04, and Ch012 images of each population of beads and EVs (n = 3) (original magnification, ×60). Scale bar: 7 μm. (E) EVs were stained with BODIPY-Texas Red and conjugated fluorescent antibodies against ANXA1 (n = 3). Data are expressed as mean ± SD. *P = 0.0194. Statistical comparisons were performed by 2-tailed Student’s t test.