Resolvin E1 is a pro‐repair mediator that promotes intestinal epithelial wound healing

Abstract

Resolution of inflammation and epithelial repair are active processes mediated by bioactive lipids known as specialized pro‐resolving mediators (SPMs). Resolvin E1 (RvE1), a SPM derived from omega‐3 fatty acid, has been reported to mediate anti‐inflammatory response in different tissues. Nevertheless, the role of RvE1 in mediating intestinal epithelial wound healing is not well understood.We identified increased RvE1 in healing colonic wounds. RvE1 treatments enhanced intestinal epithelial wound repair in‐vitro. Analysis of the signaling pathways revealed activation of pathways such as CREB, mTOR and Src‐FAK in response to RvE1 exposure. Additionally, RvE1 increased activation of the small GTPase Rac1, leading to increased intracellular reactive oxygen species (ROS) production, cell‐matrix adhesion and cellular protrusions at the leading edge of migrating cells. To harness this mechanism of repair, we performed intramucosal injection of synthetic nanoparticles containing RvE1 in injured murine colon. RvE1 nanoparticles increased wound closure compared to naked RvE1 and empty nanoparticles. In summary, the above findings provide important insight on mechanisms of intestinal mucosal wound repair driven by RvE1 and determine its potential as a therapeutic agent aimed at facilitating mucosal wound closure and epithelial barrier recovery in the intestineSupport or Funding InformationThis work was supported by a Crohn’s and Colitis Foundation Career Development Award (544599, to MQ) and NIH grants (HL127236 to AJG; DK055679, DK089763, DK059888, to AN; and DK61739, DK72564, DK79392, to CAP).