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.
Leoni, G., Neumann, P-A., Kamaly, N.
, Quiros, M., Nishio, H., Jones, H. R., Sumagin, R., Hilgarth, R. S., Alam, A., Fredman, G., Argyris, I., Rijcken, E., Kusters, D., Reutelingsperger, C., Perretti, M., Parkos, C. A., Farokhzad, O. C., Neish, A. S., & Nusrat, A. (2015). Annexin A1– containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair
. Journal of Clinical Investigation
(3), 1215-1227. https://doi.org/10.1172/JCI76693