Annexin A1-containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair
Annexin A1-containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair
复制标题
DOI：
10.1172/jci76693
复制
发表时间：
2015-03-01
影响因子：
15.9
通讯作者：
Nusrat, Asma
中科院分区：
文献类型：
--
作者：
Leoni, Giovanna;Neumann, Philipp-Alexander;Nusrat, Asma
上皮恢复是损伤后修复粘膜表面屏障功能所需的重要过程。上皮屏障功能的长期破坏导致炎症和进一步损伤;因此，更好地理解上皮恢复过程具有改善治疗方法发展的潜力。在这项工作中，我们证明了内源性膜联蛋白A1（ANXA 1）作为肠上皮细胞来源的细胞外囊泡（EV）的一种成分释放，这些含ANXA 1的EV激活伤口修复回路。与健康对照组相比，活动性炎症性肠病患者血清中分泌的含ANXA 1的EV水平升高，表明含ANXA 1的EV在炎症过程中全身分布，并可能作为肠粘膜炎症的生物标志物。包封在靶向聚合物纳米颗粒（Ac 2 -26 Col IV NP）内的外源性ANXA 1模拟肽（Ac 2 -26）的局部肠递送加速了活检诱导的损伤后鼠结肠伤口的愈合。此外，Ac 2 -26 Col IV NP的一次性全身施用加速了实验诱导的结肠炎后的恢复。总之，我们的研究结果表明，局部递送封装在纳米颗粒内的促分解肽可能代表了以慢性粘膜损伤为特征的临床情况的潜在治疗策略，例如在IBD患者中所见。
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.