title: 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
authors: G
authors: Leoni
authors: Philipp-Alexander
authors: PA
authors: Neumann
authors: Nazila
authors: N
authors: Kamaly
authors: Miguel
authors: M
authors: Quiros
authors: Hikaru
authors: H
authors: Nishio
authors: Hefin R
authors: HR
authors: Jones
authors: Ronen
authors: R
authors: Sumagin
authors: Roland S
authors: RS
authors: Hilgarth
authors: Ashfaqul
authors: A
authors: Alam
authors: Gabrielle
authors: G
authors: Fredman
authors: Ioannis
authors: I
authors: Argyris
authors: Emile
authors: E
authors: Rijcken
authors: Dennis
authors: D
authors: Kusters
authors: Chris
authors: C
authors: Reutelingsperger
authors: Mauro
authors: M
authors: Perretti
authors: Charles A
authors: CA
authors: Parkos
authors: Omid C
authors: OC
authors: Farokhzad
authors: Andrew S
authors: AS
authors: Neish
authors: Asma
authors: A
authors: Nusrat
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000008:administration & dosage / Q000502:physiology*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D002460:Cell Line; D003092:Colitis / Q000097:blood / Q000503:physiopathology; D055354:Exosomes / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000503:physiopathology*; D018345:Mice, Knockout; D053758:Nanoparticles; D010455:Peptides / Q000008:administration & dosage; D014945:Wound Healing
chemical_list: D017305:Annexin A1; D000893:Anti-Inflammatory Agents; D010455:Peptides; C096153:annexin A1 peptide (2-26)