Repair of epithelial wounds is essential for establishing intestinal mucosal homeostasis. Annexin 1 (AnxA1) promotes wound closure by activating intestinal epithelial formyl peptide receptor signaling. Here we show that AnxA1 is released from intestinal epithelial cells in extracellular vesicles (EVs). We determined that AnxA1 EV release is regulated by actin cytoskeletal dynamics and Rho GTPase signaling. EVs isolated from supernatants of epithelial cells increased reactive oxygen species generation and wound healing. Interestingly, EVs from AnxA1 null mice failed to enhance wound repair, demonstrating an important role of AnxA1 EVs in wound healing. Localized intramucosal administration of synthetic nanoparticles containing AnxA1 mimetic peptide Ac2-26 similarly promoted colonic mucosal wound repair. Epithelial derived AnxA1 EVs represent a novel mechanism regulating wound repair and local administration of synthetic vesicles containing pro-resolving peptides offer new therapeutic approaches to promote healing of intestinal mucosal ulcers
|Conference||Experimental Biology 2014|
|Period||26/04/2014 → 30/04/2014|
Quiros, M., Leoni, G., Kamaly, N.
, Neumann, P-A., Nishio, H., Fredman, G., Alam, M., Kusters, D., Reutelingsperger, C., Perretti, M., Parkos, C. A., Farokhzad, O. C., Neish, A. S., & Nusrat, A. (2014). Annexin A1 released from epithelial extracellular vesicles and synthetic nanoparticles promotes wound repair
. F A S E B Journal
(1), 1215-1227. http://www.fasebj.org/content/28/1_Supplement/488.5