Annexin A1–containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair
Year: 2015
Type: article
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.
DOI: 10.1172/jci76693
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
Institutions: Emory University, Ludwig-Maximilians-Universität München, University Hospital Münster, Brigham and Women's Hospital, Harvard University, Queen Mary University of London, William Harvey Research Institute, Columbia University, University of Münster, Maastricht University, University of Michigan
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: Brigham and Women's Hospital, Emory University, Wellcome Trust, Crohn's and Colitis Foundation, William Harvey Research Foundation, Deutsche Forschungsgemeinschaft, National Institutes of Health, Biotechnology and Biological Sciences Research Council, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: University of Michigan Center for Gastrointestinal Research, Intestinal mucosal wound resealing, G1615405189, G1750046872, Emory Epithelial Pathobiology Research Development Center, G2649407103, Structure function studies in intestinal epithelial JAM, G3283714537, Neutrophil interactions with apical ICAM-1 regulate intestinal epithelial homeost, G5070613106, G55135688, Neutrophil Interactions with Intestinal Epithelial Cells, G6302720451, G6632036768, Microbial Influence on Mucosal Homeostasis, Formyl peptide receptors as mediators of intestinal mucosal homeostasis, G9000033596, G9000307649, G9000320974, Intestinal Inflammation: Signaling proteins and the rate of PMN transmigration
OpenAlex ID: W1982159359